Prof. Dr. Dr. h.c. Christian Haass

Standortsprecher und Gruppenleiter
Prof. Dr. Haass ist Institutsleiter am Adolf-Butenandt-Institut der LMU

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Feodor-Lynen-Str. 17
81377 München

christian.haass@dzne.de
+49 (0) 89 / 4400-46550 (Sekretariat)
+49 (0) 89 / 4400-46549 (Büro)
+49 (0) 89 / 4400-46508

Curriculum Vitae

Christian Haass studierte Biologie an der Universität Heidelberg, wo er 1989 mit einer Doktorarbeit über die Klonierung der ersten Proteasom Untereinheiten promovierte.

Aufgrund seiner wissenschaftlichen Erfahrungen mit Proteasen, begann er sich für die Mechanismen der Alzheimer Erkrankung zu interessieren. Als Postdoktorand arbeitete Prof. Haass in der Gruppe von Dr. Dennis Selkoe an der Harvard Medical School (1990-1992), wo er anschließend zum Assistant Professor of Neurology (1992-1995) berufen wurde.

1995 kehrte Prof. Haass nach Deutschland zurück und leitete bis 1999 in Mannheim die Abteilung Molekulare Biologie am Zentralinstitut für Seelische Gesundheit (ZI). 1999 wurde er zum Professor für Stoffwechselbiochemie an die Ludwig-Maximilians-Universität berufen. Im gleichen Jahr initiierte Prof. Haass das erste deutschlandweite Forschungsnetzwerk zur Alzheimer-Erkrankung durch die Gründung des DFG geförderten Forschungsschwerpunktes „Zelluläre Mechanismen der Alzheimer Erkrankung“.

Im darauffolgenden Jahr wurde er Sprecher des DFG geförderten Sonderforschungsbereiches SFB 596 „Molekulare Mechanismen der Neurodegeneration“. Prof. Haass wurde mit zahlreichen Auszeichnungen geehrt, unter anderem mit dem „Gottfried Wilhelm Leibniz“ Preis der DFG, dem „Ernst Jung Preis für Medizin“, dem „Potamkin“ Preis der Amerikanischen Akademie für Neurologie, dem „Sheik Hamdan“ Preis für medizinische Wissenschaften und dem „MetLife Foundation“ Preis für medizinische Forschung. Im Jahre 2010 verlieh ihm die medizinische Fakultät der Universität Zürich die Ehrendoktorwürde. 2012 wurde Haass vom Europäischen Forschungsrat (ERC) mit einem bis zu 2,5 Millionen Euro dotierten Advanced Investigator Grant ausgezeichnet.

Prof. Haass ist Mitglied der European Molecular Biology Organization (EMBO) und der Deutschen Akademie der Naturforscher Leopoldina. Er ist Mitglied des Editorial Boards des EMBO Journals, EMBO Reports, EMBO Molecular Medicine und Science.

Publikationen

Publikationen

Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS.

Dormann D, Madl T, Valori CF, Bentmann E, Tahirovic S, Abou-Ajram C, Kremmer E, Ansorge O, Mackenzie IR, Neumann M, Haass C. EMBO J. 2012 Sep 11. doi: 10.1038/emboj.2012.261. [Epub ahead of print]

Cellular ageing, increased mortality and FTLD-TDP-associated neuropathology in progranulin knockout mice.

Wils H, Kleinberger G, Pereson S, Janssens J, Capell A, Van Dam D, Cuijt I, Joris G, De Deyn PP, Haass C, Van Broeckhoven C, Kumar-Singh S. J Pathol. 2012 Sep;228(1):67-76. doi: 10.1002/path.4043. Epub 2012 Jun 25.

Requirements for stress granule recruitment of fused in Sarcoma (FUS) and TAR DNA binding protein of 43 kDa (TDP-43).

Bentmann E, Neumann M, Tahirovic S, Rodde R, Dormann D, Haass C. J Biol Chem. 2012 Jun 29;287(27):23079-94. Epub 2012 May 4.

Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons.

Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M, Volbracht C, Schepers U, Imhof A, Hoffmeister A, Haass C, Roßner S, Bräse S, Lichtenthaler SF. EMBO J. 2012 Jun 22;31(14):3157-68. doi: 10.1038/emboj.2012.173.

Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences.

Exner N, Lutz AK, Haass C, Winklhofer KF. EMBO J. 2012 Jun 26;31(14):3038-62. doi: 10.1038/emboj.2012.170.

Loss of fused in sarcoma (FUS) promotes pathological Tau splicing.

Orozco D, Tahirovic S, Rentzsch K, Schwenk BM, Haass C, Edbauer D. EMBO Rep. 2012 Aug 1;13(8):759-64. doi: 10.1038/embor.2012.90. Epub 2012 Jun 19.

Generation of a novel rodent model for DYT1 dystonia.

Grundmann K, Glöckle N, Martella G, Sciamanna G, Hauser TK, Yu L, Castaneda S, Pichler B, Fehrenbacher B, Schaller M, Nuscher B, Haass C, Hettich J, Yue Z, Nguyen HP, Pisani A, Riess O, Ott T. Neurobiol Dis. 2012 Jul;47(1):61-74. Epub 2012 Mar 26.

The α-Helical Content of the Transmembrane Domain of the British Dementia Protein-2 (Bri2) Determines Its Processing by Signal Peptide Peptidase-like 2b (SPPL2b).

Fluhrer R, Martin L, Klier B, Haug-Kröper M, Grammer G, Nuscher B, Haass C. J Biol Chem. 2012 Feb 10;287(7):5156-63. Epub 2011 Dec 22.

BACE1 Dependent Neuregulin Processing: Review.

Fleck D, Garratt AN, Haass C, Willem M. Curr Alzheimer Res. 2012 Feb 1;9(2):178-83.

Bace1 processing of NRG1 type III produces a myelin-inducing signal but is not essential for the stimulation of myelination.

V Velanac, T Unterbarnscheidt, W Hinrichs, MN Gummert, TM Fischer, MJ Rossner, A Trimarco, V Brivio, C Taveggia, M Willem, C Haass, W Möbius, KA Nave, MH Schwab; Glia. 2012 Feb;60(2):203-17. doi: 10.1002/glia.21255. Epub 2011 Nov 2.

Translational repression of the Disintegrin and Metalloprotease ADAM10 by a stable G-quadruplex secondary structure in its 5'-untranslated region.

S Lammich, F Kamp, J Wagner, B Nuscher, S Zilow, AK Ludwig, M Willem, C Haass; J Biol Chem. 2011 Dec 30;286(52):45063-72. Epub 2011 Nov 7.

The Nicastrin ectodomain adopts a highly thermostable structure

R Fluhrer, F Kamp, G Grammer, B Nuscher, H Steiner, K Beyer, C Haass; Biol Chem. 2011 Nov;392(11):995-1001.

Novel {gamma}-Secretase Enzyme Modulators Directly Target Presenilin Protein.

A Ebke, T Luebbers, A Fukumori, K Shirotani, C Haass, K Baumann, H Steiner;J Biol Chem. 2011 Oct 28;286(43):37181-6. Epub 2011 Sep 6.

FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations

M Neumann, E Bentmann, D Dormann, A Jawaid, M Dejesus-Hernandez, O Ansorge, S Roeber, HA Kretzschmar, DG Munoz, H Kusaka, O Yokota, L-C Ang, J Bilbao, R Rademakers, C Haass, IRA MacKenzie; Brain. 2011 Sep;134(Pt 9):2595-609. Epub 2011 Aug 19.

TDP-43 and FUS: a nuclear affair.

D Dormann, C Haass; Trends Neurosci. 2011 Jun 21. [Epub ahead of print]

Regulated intramembrane proteolysis--lessons from amyloid precursor protein processing.

SF Lichtenthaler, C Haass, H Steiner; J Neurochem. 2011 Jun;117(5):779-96. doi: 10.1111/j.1471-4159.2011.07248.x. Epub 2011 Apr 14.

Rescue of Progranulin Deficiency Associated with Frontotemporal Lobar Degeneration by Alkalizing Reagents and Inhibition of Vacuolar ATPase.

A Capell, S Liebscher, K Fellerer, N Brouwers, M Willem, S Lammich, I Gijselinck, T Bittner, AM Carlson, F Sasse, B Kunze, H Steinmetz, R Jansen, D Dormann, K Sleegers, M Cruts, J Herms, C Van Broeckhoven, C Haass; J Neurosci. 2011 Feb 2.

Amyloid-β protein modulates the perivascular clearance of neuronal apolipoprotein E in mouse models of Alzheimer's disease.

Rolyan H, Feike AC, Upadhaya AR, Waha A, Van Dooren T, Haass C, Birkenmeier G, Pietrzik CU, Van Leuven F, Thal DR, J Neural Transm. 2011 May;118(5):699-712. Epub 2011 Jan 6.

Attenuated Abeta42 responses to low potency gamma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds.

B Kretner, A Fukumori, A Gutsmiedl, RM Page, T Luebbers, G Galley, K Baumann, C Haass, H Steiner; J Biol Chem. 2011 Apr 29;286(17):15240-51. Epub 2011 Feb 25.

Initiation and propagation of neurodegeneration.

C. Haass; Nat Med. 2010 Nov;16(11):1201-4. Epub 2010 Sep 21.

Boxing-acute complications and late sequelae: from concussion to dementia.

H Förstl, C Haass, B Hemmer, B Meyer, M Halle; Dtsch Arztebl Int. 2010 Nov;107(47):835-9. Epub 2010 Nov 26.

Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1.

Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, Brunner B, Nuscher B, Bartels T, Giese A, Beyer K, Eimer S, Winklhofer KF, Haass C. (2010), EMBO J. 2010 Oct 20;29(20):3571-89. Epub 2010 Sep 14.

The N-terminus of the intrinsically disordered protein α-synuclein triggers membrane binding and helix folding.

Bartels T, Ahlstrom LS, Leftin A, Kamp F, Haass C, Brown MF, Beyer K (2010), Biophys J. 2010 Oct 6;99(7):2116-24.

Fyn-tau-amyloid: a toxic triad.

C Haass, E Mandelkow; Cell. 2010 Aug 6;142(3):356-8.

Parkin is protective against proteotoxic stress in a transgenic zebrafish model

ME Fett, A Pilsl, D Paquet, F van Bebber, C Haass, J Tatzelt, B Schmid, KF Winklhofer; PLoS One. 2010 Jul 30;5(7):e11783.

Bepridil and Amiodarone Simultaneously Target the Alzheimer’s Disease beta- and gamma-Secretase via Distinct Mechanisms.

S Mitterreiter, RM Page, F Kamp, J Hopson,E Winkler, HR Ha, R Hamid, J Herms, TU Mayer, DJ Nelson, H Steiner, T Stahl, U Zeitschel, S Rossner, C Haass, SF Lichtenthaler; J. Neurosci. 2010 Jun 30; 30(26): 8974–83.

Beta-amyloid precursor protein mutants respond to gamma-secretase modulators.

RM Page, A Gutsmiedl, A Fukumori, E Winkler, C Haass, H Steiner; J Biol Chem. 2010 Jun 4; 285(23): 17798-810. Epub 2010 Mar 26.

ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.

Dormann, D, Rodde, R, Edbauer, D, Bentmann, E, Fischer, I, Hruscha, A, Than ME, Mackenzie I RA, Capell A, Schmid S, Neumann M, Haass, C. (2010), EMBO J.,29, 2841-2857.

The transmembrane protein 147 (TMEM 147) is a novel component of the nicalin-nomo complex.

Dettmer U, Kuhn PH, Abou-Ajram C, Lichtenthaler SF, Krueger M, Kremmer E, Haass C, Haffner C, J Biol Chem., 285, 26174-26181.

Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of γ-secretase-mediated intramembrane proteolysis.

Fukumori, A., Fluhrer, R., Steiner, H., and Haass, C. (2010), J. Neuroscience 30, 7853-7862.

Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5' untranslated region.

Lammich, S., Buell, D., Zilow, S., Ludwig, A.-K., Nuscher, B., Lichtenthaler, S., Prinzen, C., Fahrenholz, F. and Haass, C. (2010), J. Biol. Chem. 285, 15763 - 15760.

Methylene Blue fails to inhibit Tau and Polyglutamine Protein dependent toxicity in Zebrafish.

van Bebber, F., Paquet, D., Hruscha, A., Schmid, B. and Haass, C. (2010), Neurobiol Dis. 2010 Sep;39(3):265-71. Epub 2010 Apr 8

Transgenic Zebrafish as a Novel Animal Model to Study Tauopathies and Other Neurodegenerative Disorders in vivo.

Paquet D, Schmid B, Haass C.; Neurodegener Dis. 2010;7(1-3):99-102. Epub 2010 Feb 18.

Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavage

BI Perez-Revuelta, A Fukumori, S Lammich, A Yamasaki, C Haass, H Steiner; J Neurochem. 2010 Feb 10; 112(4):940-50

Masking of transmembrane-based retention signals controls ER export of gamma-secretase.

M Fassler, M Zocher, S Klare, AG de la Fuente, J Scheuermann, A Capell, C Haass, C Valkova, A Veerappan, D Schneider, C Kaether; Traffic. 2010 Feb;11(2):250-8. Epub 2009 Nov 5.

APP mutants respond to γ-secretase modulators.

Page, R., Gutsmiedl, A., Fukumori, A., Winkler, E., Haass, C. and Steiner, H. (2010), J. Biol. Chem. 285, 17798 - 17810.

Microglia Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease.

Fuhrmann, M., Bittner, T., Jung, C., Burgold, S., Page, R. Mitteregger, G., Haass, C., LaFerla, F., Kretzschmar, H. and Herms, J. (2010), Nature Neuroscience 13, 411 - 413. 

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor.

Itoh N, Okochi M, Tagami S, Nishitomi K, Nakayama T, Yanagida K, Fukumori A, Jiang J, Mori K, Hosono M, Kikuchi J, Nakano Y, Takinami Y, Dohi K, Nishigaki A, Takemoto H, Minagawa K, Katoh T, Willem M, Haass C, Morihara T, Tanaka T, Kudo T, Hasegawa H, Nishimura M, Sakaguchi G, Kato A, Takeda M. (2009), Neurodegener Dis. 2009;6(5-6):230-9. Epub 2009 Sep 9.

Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway.

T Bittner, M Fuhrmann, S Burgold, CK Jung, C Volbracht, H Steiner, G Mitteregger, HA Kretzschmar, C Haass, J Herms; J Neurosci. 2009 Aug 19;29(33):10405-9.

Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin.

D Dormann, A Capell, AM Carlson, SS Shankaran, R Rodde, M Neumann, E Kremmer, T Matsuwaki, K Yamanouchi, M Nishihara, C Haass C; J Neurochem. 2009 Aug; 110(3):1082-94. Epub 2009 Jun 9.

A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation.

D Paquet, R Bhat, A Sydow, EM Mandelkow, S Berg, S Hellberg, J Fälting, M Distel, RW Köster, B Schmid, C Haass; J Clin Invest. 2009 May; 119(5): 1382-95. doi: 10.1172/JCI37537. Epub 2009 Apr 13.

Mitochondrial dysfunction in Parkinson's disease.

Winklhofer KF, Haass C. (2009), Biochim Biophys Acta, 1802, 29 -44.

Parkin deficiency delays motor decline and disease manifestation in a mouse model of synucleinopathy.

Fournier M, Vitte J, Garrigue J, Langui D, Dullin JP, Saurini F, Hanoun N, Perez-Diaz F, Cornilleau F, Joubert C, Ardila-Osorio H, Traver S, Duchateau R, Goujet-Zalc C, Paleologou K, Lashuel HA, Haass C, Duyckaerts C, Cohen-Salmon C, Kahle PJ, Hamon M, Brice A, Corti O. (2009), PLoS One, 4: e6629

gamma-Secretase inhibition reduces spine density in vivo via an amyloid precursor protein dependent pathway

Bittner T, Fuhrmann M, Burgold S, Jung CK, Volbracht C, Steiner H, Mitteregger G, Kretzschmar HA, Haass C, Herms J (2009), J. Neuroscience 19, 10405 - 10409.

Loss of parkin or PINK1 function increases DRP1-dependent mitochondrial fragmentation.

Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Laemmermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, Bouman L, Vogt-Weisenhorn D, Wurst W, Tatzelt J, Haass C, Winklhofer KF (2009), J. Biol. Chem., 284, 22938 - 22951.

Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin.

Dormann D, Capell A, Carlson AM, Shankaran SS, Rodde R, Neumann M, Kremmer E, Matsuwaki T, Yamanouchi K, Nishihara M, Haass C. (2009)  J. Neurochem., 110, 1082 - 1094.

Function, regulation and therapeutic properties of beta-secretase (BACE1) (2009)

Willem M, Lammich S, Haass C. (2009), Semin Cell Dev Biol., 20, 175-82.

Gal4-UAS based transgenic expression of amyloidogenic proteins allows early detection of disease specific neuropathology in zebrafish.

Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, Fälting J, Distel M, Köster RW, Schmid B, Haass C. (2009), J. Clinical Investigation, 119, 1382 - 1395.

Purification, Pharmacological Modulation, and Biochemical Characterization of Interactors of Endogenous Human γ-Secretase.

Winkler E, Hobson S, Fukumori A, Dümpelfeld B, Luebbers T, Baumann K, Haass C, Hopf C and Steiner H (2009), Biochemistry 48, 1183 - 1197.

Intramembrane proteolysis by signal peptidepeptidases - a comparative discussion of GxGD -type aspartyl proteases.

Fluhrer R, Steiner H and Haass C. (2009), J Biol Chem. 284, 13975 - 13979.

Substrate requirements for SPPL2b dependent intramembrane proteolysis.

Martin, L., Fluhrer, R. and Haass, C. (2009), J. Biol. Chem. 284, 5662-5670.

Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis.

O'Connor T, Sadleir KR, Maus E, Velliquette RA, Zhao J, Cole SL, Eimer WA, Hitt B, Bembinster LA, Lammich S, Lichtenthaler SF, Hébert SS, De Strooper B, Haass C, Bennett DA, Vassar R (2008), Neuron 60; 988-1009.

Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.

Busche, M.A., Eichhoff, G., Adelsberger, H., Abramowski, D., Wiederhold, K.H., Haass, C., Staufenbiel, M., Konnerth, A., and Garaschuk, O. (2008), Science 321, 1686-1689.

Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment.

Dejaegere, T., Serneels, L., Schafer, M.K., Van Biervliet, J., Horre, K., Depboylu, C., Alvarez-Fischer, D., Herreman, A., Willem, M., Haass, C., Höglinger, G.U., Hooge, R.D., and De Strooper, B. (2008), Proc Natl Acad Sci U S A 105, 9775-9780.

Intramembrane proteolysis of GxGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutation.

Fluhrer, R., Fukumori, A., Martin, L., Grammer, G., Haug-Kroper, M., Klier, B., Winkler, E., Kremmer, E., Condron, M.M., Teplow, D.B., Steiner, H., and Haass, C. (2008), J. Biol Chem., 283, 30121-8.

Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b.

Martin, L., Fluhrer, R., Reiss, K., Kremmer, E., Saftig, P., and Haass, C. (2008), J. Biol. Chem. 283, 1644-1652.

Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation.

Page, R.M., Baumann, K., Tomioka, M., Perez-Revuelta, B.I., Fukumori, A., Jacobsen, H., Flohr, A., Luebbers, T., Ozmen, L., Steiner, H., and Haass, C. (2008), J. Biol. Chem. 283, 677-683.

A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein.

Schobel, S., Neumann, S., Hertweck, M., Dislich, B., Kuhn, P.H., Kremmer, E., Seed, B., Baumeister, R., Haass, C., and Lichtenthaler, S.F. (2008), J. Biol. Chem. 283, 14257-14268.

Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion.

Shankaran, S.S., Capell, A., Hruscha, A.T., Fellerer, K., Neumann, M., Schmid, B., and Haass, C. (2008), J. Biol. Chem. 283, 1744-1753.

Regulatory RNA goes awry in Alzheimer's disease.

St George-Hyslop, P., and Haass, C. (2008), Nat. Med. 14, 711-712.

Intramembrane proteolysis by gamma-secretase.

Steiner, H., Fluhrer, R., and Haass, C. (2008), J. Biol. Chem. 283, 29627 - 31.

Chemical crosslinking provides a model of the gamma -secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1.

Steiner, H., Winkler, E., and Haass, C. (2008), J Biol. Chem. 28, 34677-86.

The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases.

Winklhofer, K.F., Tatzelt, J., and Haass, C. (2008), EMBO J. 27, 336-349.

Active gamma -secretase complexes contain only one of each component.

Sato, T., Diehl, T.S., Narayanan, S., Funamoto, S., Ihara, Y., De Strooper, B., Steiner, H., Haass, C. and Wolfe, M.S. (2007), J Biol Chem., 282, 33985 - 33993

Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content.

Hamid R, Kilger E, Willem M, Vassallo N, Kostka M, Bornhövd C, Reichert AS, Kretzschmar HA, Haass C, Herms J. (2007), J Neurochem. 102, 1264-1275.

Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin.

Exner, N., Treske, B., Paquet, D., Holmstrom, K., Schiesling, C., Gispert, S., Carballo-Carbajal, I., Berg, D., Hoepken, H. H., Gasser, T., Krüger R., Winklhofer K.F., Vogel, F., Reichert, A.S., Auburger, G., Kahle, P.J., Schmid, B., and Haass, C. (2007), J Neurosci 27, 12413-12418.

Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice.

Freichel, C., Neumann, M., Ballard, T., Muller, V., Woolley, M., Ozmen, L., Borroni, E., Kretzschmar, H.A., Haass, C., Spooren, W. and Kahle, P.J. (2007), Neurobiol Aging 28, 1421-35.

Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in perivascular drainage channels of wild-type andAPP-transgenic mice.

Thal, D.R., Larionov, S., Abramowski, D., Wiederhold, K.H., Van Dooren, T., Yamaguchi, H., Haass, C., Van Leuven, F., Staufenbiel, M. and Capetillo-Zarate, E. (2007), Neurobiol Aging 28, 1221-30.

Endoplasmic reticulum retention of the gamma-secretase complex component Pen2 by Rer1.

Kaether, C., Scheuermann, J., Fassler, M., Zilow, S., Shirotani, K., Valkova, C., Novak, B., Kacmar, S., Steiner, H. and Haass, C. (2007), EMBO Rep 8, 743-8.

Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content.

Hamid, R., Kilger, E., Willem, M., Vassallo, N., Kostka, M., Bornhovd, C., Reichert, A.S., Kretzschmar, H.A., Haass, C. and Herms, J. (2007), J Neurochem 102, 1264-75.

Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes.

Shirotani, K., Tomioka, M., Kremmer, E., Haass, C. and Steiner, H. (2007), Neurobiol Dis 27, 102-7.

A structural switch of presenilin 1 by glycogen synthase kinase 3beta-mediated phosphorylation regulates the interaction with beta-catenin and its nuclear signaling.

Prager, K., Wang-Eckhardt, L., Fluhrer, R., Killick, R., Barth, E., Hampel, H., Haass, C. and Walter, J. (2007), J Biol Chem 282, 14083-93.

Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1.

Gorner, K., Holtorf, E., Waak, J., Pham, T.T., Vogt-Weisenhorn, D.M., Wurst, W., Haass, C. and Kahle, P.J. (2007), J Biol Chem 282, 13680-91.

Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta-, and gamma-secretase.

Kuhn, P.H., Marjaux, E., Imhof, A., De Strooper, B., Haass, C. and Lichtenthaler, S.F. (2007), J Biol Chem 282, 11982-95.

The Nicastrin-like protein Nicalin regulates assembly and stability of the Nicalin-nodal modulator (NOMO) membrane protein complex.

Haffner, C., Dettmer, U., Weiler, T. and Haass, C. (2007), J Biol Chem 282, 10632-8.

Identification of anti-prion compounds as efficient inhibitors of polyglutamine protein aggregation in a zebrafish model.

Schiffer, N.W., Broadley, S.A., Hirschberger, T., Tavan, P., Kretzschmar, H.A., Giese, A., Haass, C., Hartl, F.U. and Schmid, B. (2007), J Biol Chem 282, 9195-203.

Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.

Haass, C. and Selkoe, D.J. (2007), Nat Rev Mol Cell Biol 8, 101-12.

N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma-secretase.

Narlawar, R., Perez Revuelta, B.I., Baumann, K., Schubenel, R., Haass, C., Steiner, H. and Schmidt, B. (2007), Bioorg Med Chem Lett 17, 176-82.

Signal peptide peptidases and gamma-secretase: cousins of the same protease family?

Fluhrer, R. and Haass, C. (2007), Neurodegener Dis 4, 112-6.

Scaffold of thecyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators.

Narlawar, R., Perez Revuelta, B.I., Haass, C., Steiner, H., Schmidt, B. and Baumann, K. (2006), J Med Chem 49, 7588-91.

Selective vulnerability of different types of commissural neurons for amyloid beta-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology.

Capetillo-Zarate, E., Staufenbiel, M., Abramowski, D., Haass, C., Escher, A., Stadelmann, C., Yamaguchi, H., Wiestler, O.D. and Thal, D.R. (2006), Brain 129, 2992-3005.

Control of peripheral nerve myelination by the beta-secretase BACE1.

Willem, M., Garratt, A.N., Novak, B., Citron, M., Kaufmann, S., Rittger, A., DeStrooper, B., Saftig, P., Birchmeier, C. and Haass, C. (2006), Science 314, 664-6.

Pore-forming scissors? A first structural glimpse of gamma-secretase.

Steiner, H., Than, M., Bode, W. and Haass, C. (2006), Trends Biochem Sci 31, 491-3.

Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

Radde, R., Bolmont, T., Kaeser, S.A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M.E., Jaggi, F., Wolburg, H., Gengler, S., Haass, C., Ghetti, B., Czech, C., Holscher, C., Mathews, P.M. and Jucker, M. (2006), EMBO Rep 7, 940-6.

A basolateral sorting signal directs ADAM10 to adherens junctions and is required for its function in cell migration.

Wild-Bode, C., Fellerer, K., Kugler, J., Haass, C. and Capell, A. (2006), J Biol Chem 281, 23824-9.

A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b.

Fluhrer, R., Grammer, G., Israel, L., Condron, M.M., Haffner, C., Friedmann, E., Bohland, C., Imhof, A., Martoglio, B., Teplow, D.B. and Haass, C. (2006), Nat Cell Biol 8, 894-6.

Inhibition of APP trafficking by tau protein does not increase the generation of amyloid-beta peptides.

Goldsbury, C., Mocanu, M.M., Thies, E., Kaether, C., Haass, C., Keller, P., Biernat, J., Mandelkow, E. and Mandelkow, E.M. (2006), Traffic 7, 873-88.

European Alzheimer disease funding.

Haass, C. (2006), Nat Med 12, 776-7.

SorLA signaling by regulated intramembrane proteolysis.

Bohm, C., Seibel, N.M., Henkel, B., Steiner, H., Haass, C. and Hampe, W. (2006), J Biol Chem 281, 14547-53.

Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin's transcriptional activity.

Anders, L., Mertins, P., Lammich, S., Murgia, M., Hartmann, D., Saftig, P., Haass, C. and Ullrich, A. (2006), Mol Cell Biol 26, 3917-34.

Presenilin-dependent gamma-secretase on plasma membrane and endosomes is functionally distinct.

Fukumori, A., Okochi, M., Tagami, S., Jiang, J., Itoh, N., Nakayama, T., Yanagida, K., Ishizuka-Katsura, Y., Morihara, T., Kamino, K., Tanaka, T., Kudo, T., Tanii, H., Ikuta, A., Haass, C. and Takeda, M. (2006), Biochemistry 45, 4907-14.

The GxGD motif of presenilin contributes to catalytic function and substrate identification of gamma-secretase.

Yamasaki, A., Eimer, S., Okochi, M., Smialowska, A., Kaether, C., Baumeister, R., Haass, C. and Steiner, H. (2006), J Neurosci 26, 3821-8.

Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface.

Kaether, C., Schmitt, S., Willem, M. and Haass, C. (2006), Traffic 7, 408-15.

Secretion of the Notch-1 Abeta-like peptide during Notch signaling.

Okochi, M., Fukumori, A., Jiang, J., Itoh, N., Kimura, R., Steiner, H., Haass, C., Tagami, S. and Takeda, M. (2006), J Biol Chem 281, 7890-8.

Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein.

Neumann, S., Schobel, S., Jager, S., Trautwein, A., Haass, C., Pietrzik, C.U. and Lichtenthaler, S.F. (2006), J Biol Chem 281, 7583-94.

Assembly, trafficking and function of gamma-secretase.

Kaether, C., Haass, C. and Steiner, H. (2006), Neurodegener Dis 3, 275-83.

Cellular functions of gamma-secretase-related proteins.

Haffner, C. and Haass, C. (2006), Neurodegener Dis 3, 284-9.

Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3.

Krawitz, P., Haffner, C., Fluhrer, R., Steiner, H., Schmid, B. and Haass, C. (2005), J Biol Chem 280, 39515-23.

Apolipoprotein E co-localizes with newly formed amyloid beta-protein (Abeta) deposits lacking immunoreactivity against N-terminal epitopes of Abeta in a genotype-dependent manner.

Thal, D.R., Capetillo-Zarate, E., Schultz, C., Rub, U., Saido, T.C., Yamaguchi, H., Haass, C., Griffin, W.S., Del Tredici, K., Braak, H. and Ghebremedhin, E. (2005), Acta Neuropathol (Berl) 110, 459-71.

Stable chromosomal association of MSL2 defines a dosage-compensated nuclear compartment.

Straub, T., Neumann, M.F., Prestel, M., Kremmer, E., Kaether, C., Haass, C. and Becker, P.B. (2005), Chromosoma 114, 352-64.

Single particle detection and characterization of synuclein co-aggregation.

Giese, A., Bader, B., Bieschke, J., Schaffar, G., Odoy, S., Kahle, P.J., Haass, C. and Kretzschmar, H. (2005), Biochem Biophys Res Commun 333, 1202-10.

GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network.

Wahle, T., Prager, K., Raffler, N., Haass, C., Famulok, M. and Walter, J. (2005), Mol Cell Neurosci 29,
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Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments.

Prokop, S., Haass, C. and Steiner, H. (2005), J Neurochem 94, 57-62.

Shedding and gamma-secretase-mediated intramembrane proteolysis of the mucin-type molecule CD43.

Andersson, C.X., Fernandez-Rodriguez, J., Laos, S., Baeckstrom, D., Haass, C. and Hansson, G.C. (2005), Biochem J 387, 377-84.

Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy.

Stefanova, N., Reindl, M., Neumann, M., Haass, C., Poewe, W., Kahle, P.J. and Wenning, G.K. (2005), Am J Pathol 166, 869-76.

Gamma-secretase complex assembly within the early secretory pathway.

Capell, A., Beher, D., Prokop, S., Steiner, H., Kaether, C., Shearman, M.S. and Haass, C. (2005), J Biol Chem 280, 6471-8.

A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein.

Uelhoff, A., Tatzelt, J., Aguzzi, A., Winklhofer, K.F. and Haass, C. (2005), J Biol Chem 280, 5137-40.

Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity.

Yamamoto, A., Friedlein, A., Imai, Y., Takahashi, R., Kahle, P.J. and Haass, C. (2005), J Biol Chem 280, 3390-9.

Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme.

Westmeyer, G.G., Willem, M., Lichtenthaler, S.F., Lurman, G., Multhaup, G., Assfalg-Machleidt, I., Reiss, K., Saftig, P. and Haass, C. (2004), J Biol Chem 279, 53205-12.

The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity.

Kaether, C., Capell, A., Edbauer, D., Winkler, E., Novak, B., Steiner, H. and Haass, C. (2004), EMBO J 23, 4738-48.

A lipid boundary separates APP and secretases and limits amyloid beta-peptide generation.

Kaether, C. and Haass, C. (2004), J Cell Biol 167, 809-12.

Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stage.

Neumann, M., Muller, V., Kretzschmar, H.A., Haass, C. and Kahle, P.J. (2004), J Neuropathol Exp Neurol 63, 1225-35.

Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis.

Keil, U., Bonert, A., Marques, C.A., Scherping, I., Weyermann, J., Strosznajder, J.B., Muller-Spahn, F., Haass, C., Czech, C., Pradier, L., Muller, W.E. and Eckert, A. (2004), J Biol Chem 279, 50310-20.

beta-site amyloid precursor protein cleaving enzyme 1 increases amyloid deposition in brain parenchyma but reduces cerebrovascular amyloid angiopathy in aging BACE x APP[V717I] double-transgenic mice.

Willem, M., Dewachter, I., Smyth, N., Van Dooren, T., Borghgraef, P., Haass, C. and Van Leuven, F. (2004), Am J Pathol 165, 1621-31.

Identification of distinct gamma-secretase complexes with different APH-1 variants.

Shirotani, K., Edbauer, D., Prokop, S., Haass, C. and Steiner, H. (2004), J Biol Chem 279, 41340-5.

Human BACE forms dimers and colocalizes with APP.

Schmechel, A., Strauss, M., Schlicksupp, A., Pipkorn, R., Haass, C., Bayer, T.A. and Multhaup, G. (2004), J Biol Chem 279, 39710-7.

Co-expression of nicastrin and presenilin rescues a loss of function mutant of APH-1.

Edbauer, D., Kaether, C., Steiner, H. and Haass, C. (2004), J Biol Chem 279, 37311-5.

Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.

Haffner, C., Frauli, M., Topp, S., Irmler, M., Hofmann, K., Regula, J.T., Bally-Cuif, L. and Haass, C. (2004), EMBO J 23, 3041-50.

How does parkin ligate ubiquitin to Parkinson's disease?

Kahle, P.J. and Haass, C. (2004), EMBO Rep 5, 681-5.

Immature nicastrin stabilizes APH-1 independent of PEN-2 and presenilin: identification of nicastrin mutants that selectively interact with APH-1.

Shirotani, K., Edbauer, D., Kostka, M., Steiner, H. and Haass, C. (2004), J Neurochem 89, 1520-7.

Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease.

Neumann, M., Muller, V., Gorner, K., Kretzschmar, H.A., Haass, C. and Kahle, P.J. (2004), Acta Neuropathol (Berl) 107, 489-96.

Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region.

Lammich, S., Schobel, S., Zimmer, A.K., Lichtenthaler, S.F. and Haass, C. (2004), EMBO Rep 5, 620-5.

Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex.

Prokop, S., Shirotani, K., Edbauer, D., Haass, C. and Steiner, H. (2004), J Biol Chem 279, 23255-61.

Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics study.

Nuscher, B., Kamp, F., Mehnert, T., Odoy, S., Haass, C., Kahle, P.J. and Beyer, K. (2004), J Biol Chem 279, 21966-75.

Amyloid at the cutting edge: activation of alpha-secretase prevents amyloidogenesis in an Alzheimer disease mouse model.

Lichtenthaler, S.F. and Haass, C. (2004), J Clin Invest 113, 1384-7.

Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1.

Gorner, K., Holtorf, E., Odoy, S., Nuscher, B., Yamamoto, A., Regula, J.T., Beyer, K., Haass, C. and Kahle, P.J. (2004), J Biol Chem 279, 6943-51.

Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation.

Haass, C. (2004), EMBO J 23, 483-8.

Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis.

Fluhrer, R., Friedlein, A., Haass, C. and Walter, J. (2004), J Biol Chem 279, 1585-93.

The biochemical and genetic odyssey to the function of a nicastrin-like protein.

Haffner, C. and Haass, C. (2004), Neurodegener Dis 1, 192-5.

Nicastrin interacts with gamma-secretase complex components via the N-terminal part of its transmembrane domain.

Capell, A., Kaether, C., Edbauer, D., Shirotani, K., Merkl, S., Steiner, H. and Haass, C. (2003), J Biol Chem 278, 52519-23.

The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1.

Lichtenthaler, S.F., Dominguez, D.I., Westmeyer, G.G., Reiss, K., Haass, C., Saftig, P., De Strooper, B. and Seed, B. (2003), J Biol Chem 278, 48713-9.

Games played by rogue proteins in prion disorders and Alzheimer's disease.

Aguzzi, A. and Haass, C. (2003), Science 302, 814-8.

Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation: oxidative stress, caspases, and the JNK pathway.

Marques, C.A., Keil, U., Bonert, A., Steiner, B., Haass, C., Muller, W.E. and Eckert, A. (2003), J Biol Chem 278, 28294-302.

Potential link between amyloid beta-protein 42 and C-terminal fragment gamma 49-99 of beta-amyloid precursor protein.

Sato, T., Dohmae, N., Qi, Y., Kakuda, N., Misonou, H., Mitsumori, R., Maruyama, H., Koo, E.H., Haass, C., Takio, K., Morishima-Kawashima, M., Ishiura, S. and Ihara, Y. (2003), J Biol Chem 278, 24294-301.

Gamma-secretase activity is associated with a conformational change of nicastrin.

Shirotani, K., Edbauer, D., Capell, A., Schmitz, J., Steiner, H. and Haass, C. (2003), J Biol Chem 278, 16474-7.

Reconstitution of gamma-secretase activity.

Edbauer, D., Winkler, E., Regula, J.T., Pesold, B., Steiner, H. and Haass, C. (2003), Nat Cell Biol 5, 486-8.

Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generation.

Fluhrer, R., Multhaup, G., Schlicksupp, A., Okochi, M., Takeda, M., Lammich, S., Willem, M., Westmeyer, G., Bode, W., Walter, J. and Haass, C. (2003), J Biol Chem 278, 5531 -8.

Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts.

Ehehalt, R., Keller, P., Haass, C., Thiele, C. and Simons, K. (2003), J Cell Biol 160, 113-23.

Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases.

Haass, C. and Steiner, H. (2002), Trends Cell Biol 12, 556-62.

Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide.

Lammich, S., Okochi, M., Takeda, M., Kaether, C., Capell, A., Zimmer, A.K., Edbauer, D., Walter, J., Steiner, H. and Haass, C. (2002), J Biol Chem 277, 44754-9.

Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies.

Neumann, M., Kahle, P.J., Giasson, B.I., Ozmen, L., Borroni, E., Spooren, W., Muller, V., Odoy, S., Fujiwara, H., Hasegawa, M., Iwatsubo, T., Trojanowski, J.Q., Kretzschmar, H.A. and Haass, C. (2002), J Clin Invest 110, 1429-39.

New hope for Alzheimer disease vaccine.

Haass, C. (2002), Nat Med 8, 1195-6.

PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin.

Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M. and Haass, C. (2002), J Biol Chem 277, 39062-5.

Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1.

Okochi, M., Steiner, H., Fukumori, A., Tanii, H., Tomita, T., Tanaka, T., Iwatsubo, T., Kudo, T., Takeda, M. and Haass, C. (2002), EMBO J 21, 5408-16.

Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane.

Kaether, C., Lammich, S., Edbauer, D., Ertl, M., Rietdorf, J., Capell, A., Steiner, H. and Haass, C. (2002), J Cell Biol 158, 551-61.

Structure/function of alpha-synuclein in health and disease: rational development of animal models for Parkinson's and related diseases.

Kahle, P.J., Haass, C., Kretzschmar, H.A. and Neumann, M. (2002), J Neurochem 82, 449-57.

A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish.

Geling, A., Steiner, H., Willem, M., Bally-Cuif, L. and Haass, C. (2002), EMBO Rep 3, 688-94.

Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.

Edbauer, D., Winkler, E., Haass, C. and Steiner, H. (2002), Proc Natl Acad Sci U S A 99, 8666-71.

Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production.

Moehlmann, T., Winkler, E., Xia, X., Edbauer, D., Murrell, J., Capell, A., Kaether, C., Zheng, H., Ghetti, B., Haass, C. and Steiner, H. (2002), Proc Natl Acad Sci U S A 99, 8025-30.

Reduction of trophic support enhances apoptosis in PC12 cells expressing Alzheimer's APP mutation and sensitizes cells to staurosporine-induced cell death.

Leutz, S., Steiner, B., Marques, C.A., Haass, C., Muller, W.E. and Eckert, A. (2002), J Mol Neurosci 18, 189-201.

Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes.

Kahle, P.J., Neumann, M., Ozmen, L., Muller, V., Jacobsen, H., Spooren, W., Fuss, B., Mallon, B., Macklin, W.B., Fujiwara, H., Hasegawa, M., Iwatsubo, T., Kretzschmar, H.A. and Haass, C. (2002), EMBO Rep 3, 583-8.

A non-amyloidogenic function of BACE-2 in the secretory pathway.

Fluhrer, R., Capell, A., Westmeyer, G., Willem, M., Hartung, B., Condron, M.M., Teplow, D.B., Haass, C. and Walter, J. (2002), J Neurochem 81, 1011-20.

Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD).

Edbauer, D., Willem, M., Lammich, S., Steiner, H. and Haass, C. (2002), J Biol Chem 277,
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Apical sorting of beta-secretase limits amyloid beta-peptide production.

Capell, A., Meyn, L., Fluhrer, R., Teplow, D.B., Walter, J. and Haass, C. (2002), J Biol Chem 277, 5637-43.

UV light-induced autofluorescence of full-length Abeta-protein deposits in the human brain.

Thal, D.R., Ghebremedhin, E., Haass, C. and Schultz, C. (2002), Clin Neuropathol 21, 35-40.

Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model.

Kahle, P.J., Neumann, M., Ozmen, L., Muller, V., Odoy, S., Okamoto, N., Jacobsen, H., Iwatsubo, T., Trojanowski, J.Q., Takahashi, H., Wakabayashi, K., Bogdanovic, N., Riederer, P., Kretzschmar, H.A. and Haass, C. (2001), Am J Pathol 159, 2215-25.

The cell biology of Alzheimer's disease: uncovering the secrets of secretases.

Walter, J., Kaether, C., Steiner, H. and Haass, C. (2001), Curr Opin Neurobiol 11, 585-90.

Nuclear signaling: a common function of presenilin substrates?

Steiner, H. and Haass, C. (2001), J Mol Neurosci 17, 193-8.

Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch.

Sastre, M., Steiner, H., Fuchs, K., Capell, A., Multhaup, G., Condron, M.M., Teplow, D.B. and Haass, C. (2001), EMBO Rep 2, 835-41.

Protofibrils, the unifying toxic molecule of neurodegenerative disorders?

Haass, C. and Steiner, H. (2001), Nat Neurosci 4, 859-60.

Endoproteolysis of the ER stress transducer ATF6 in the presence of functionally inactive presenilins.

Steiner, H., Winkler, E., Shearman, M.S., Prywes, R. and Haass, C. (2001), Neurobiol Dis 8, 717-22.

Neuroscience. Parkin and its substrates.

Haass, C. and Kahle, P.J. (2001), Science 293, 224-5.

Phosphorylation regulates intracellular trafficking of beta-secretase.

Walter, J., Fluhrer, R., Hartung, B., Willem, M., Kaether, C., Capell, A., Lammich, S., Multhaup, G. and Haass, C. (2001), J Biol Chem 276, 14634-41.

Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant alpha-synuclein transgenic mice.

Rathke-Hartlieb, S., Kahle, P.J., Neumann, M., Ozmen, L., Haid, S., Okochi, M., Haass, C. and Schulz, J.B. (2001), J Neurochem 77, 1181-4.

Elevated vulnerability to oxidative stress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation.

Eckert, A., Steiner, B., Marques, C., Leutz, S., Romig, H., Haass, C. and Muller, W.E. (2001), J Neurosci Res 64, 183-92.

A pathogenic presenilin-1 deletion causes abberrant Abeta 42 production in the absence of congophilic amyloid plaques.

Steiner, H., Revesz, T., Neumann, M., Romig, H., Grim, M.G., Pesold, B., Kretzschmar, H.A., Hardy, J., Holton, J.L., Baumeister, R., Houlden, H. and Haass, C. (2001), J Biol Chem 276, 7233-9.

The Role of presenilins in gamma-secretase activity.

Wolfe, M.S. and Haass, C. (2001), J Biol Chem 276, 5413-6.

Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells.

Yamazaki, T., Chang, T.Y., Haass, C. and Ihara, Y. (2001), J Biol Chem 276, 4454-60.

The emerging utility of animal models of chronic neurodegenerative diseases.

Kahle, P.J. and Haass, C. (2001), Expert Opin Ther Targets 5, 125-32.

A loss of function mutant of the presenilin homologue SEL-12 undergoes aberrant endoproteolysis in Caenorhabditis elegans and increases abeta 42 generation in human cells.

Okochi, M., Eimer, S., Bottcher, A., Baumeister, R., Romig, H., Walter, J., Capell, A., Steiner, H. and Haass, C. (2000), J Biol Chem 275, 40925-32.

Lewy body variant of Alzheimer's disease: alpha-synuclein in dystrophic neurites of A beta plaques.

Steiner, H. and Haass, C. (2000) Intramembrane proteolysis by presenilins. Nat Rev Mol Cell Biol 1, 217-24. Wirths, O., Weickert, S., Majtenyi, K., Havas, L., Kahle, P.J., Okochi, M., Haass, C., Multhaup, G., Beyreuther, K. and Bayer, T.A. (2000), Neuroreport 11, 3737-41.

Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases.

Steiner, H., Kostka, M., Romig, H., Basset, G., Pesold, B., Hardy, J., Capell, A., Meyn, L., Grim, M.L., Baumeister, R., Fechteler, K. and Haass, C. (2000), Nat Cell Biol 2, 848-51.

Does failure of parkin-mediated ubiquitination cause juvenile parkinsonism?

Kahle, P.J., Leimer, U. and Haass, C. (2000), Trends Biochem Sci 25, 524-7.

Maturation and pro-peptide cleavage of beta-secretase.

Capell, A., Steiner, H., Willem, M., Kaiser, H., Meyer, C., Walter, J., Lammich, S., Multhaup, G. and Haass, C. (2000), J Biol Chem 275, 30849-54.

Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.

Mathews, P.M., Cataldo, A.M., Kao, B.H., Rudnicki, A.G., Qin, X., Yang, J.L., Jiang, Y., Picciano, M., Hulette, C., Lippa, C.F., Bird, T.D., Nochlin, D., Walter, J., Haass, C., Levesque, L., Fraser, P.E., Andreadis, A. and Nixon, R.A. (2000), Mol Med 6, 878-91.

Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes.

Yu, G., Chen, F., Nishimura, M., Steiner, H., Tandon, A., Kawarai, T., Arawaka, S., Supala, A., Song, Y.Q., Rogaeva, E., Holmes, E., Zhang, D.M., Milman, P., Fraser, P.E., Haass, C. and George-Hyslop, P.S. (2000), J Biol Chem 275, 27348-53.

Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain.

Kahle, P.J., Neumann, M., Ozmen, L., Muller, V., Jacobsen, H., Schindzielorz, A., Okochi, M., Leimer, U., van Der Putten, H., Probst, A., Kremmer, E., Kretzschmar, H.A. and Haass, C. (2000), J Neurosci 20, 6365-73.

Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2

Walter, J., Schindzielorz, A., Hartung, B. and Haass, C. (2000),. J Biol Chem 275, 23523-9.

Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch.

Kulic, L., Walter, J., Multhaup, G., Teplow, D.B., Baumeister, R., Romig, H., Capell, A., Steiner, H. and Haass, C. (2000), Proc Natl Acad Sci U S A 97, 5913-8.

Presenilin-1 differentially facilitates endoproteolysis of the beta-amyloid precursor protein and Notch.

Capell, A., Steiner, H., Romig, H., Keck, S., Baader, M., Grim, M.G., Baumeister, R. and Haass, C. (2000), Nat Cell Biol 2, 205-11.

Parkinson's pathology in a fly.

Haass, C. and Kahle, P.J. (2000), Nature 404, 341, 343.

Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein.

Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba, M., Iwatsubo, T., Meijer, L., Kahle, P.J. and Haass, C. (2000), J Biol Chem 275, 390-7.

Amyloid precursor protein in unique cholesterol-rich microdomains different from caveolae-like domains.

Hayashi, H., Mizuno, T., Michikawa, M., Haass, C. and Yanagisawa, K. (2000), Biochim Biophys Acta 1483, 81-90.

Mutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes.

Yu, G., Chen, F., Nishimura, M., Steiner, H., Tandon, A., Kawarai, T., Arawaka, S., Supala, A., Song, Y.Q., Rogaeva, E., Holmes, E., Zhang, D.M., Milman, P., Fraser, P., Haass, C. and St George-Hyslop, P. (2000), Acta Neurol Scand Suppl 176, 6-11

Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated protein.

Kahle, P.J., Neumann, M., Ozmen, L. and Haass, C. (2000), Ann N Y Acad Sci 920, 33-41.

Presenilin proteins and their function during embryonic development and Alzheimer's disease.

Haass, C. (2000), Ernst Schering Res Found Workshop 57-64.

An in vivo assay for the identification of target proteases which cleave membrane-associated substrates.

Steiner, H., Pesold, B. and Haass, C. (1999), FEBS Lett 463, 245-9.

Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis.

Steiner, H., Romig, H., Pesold, B., Philipp, U., Baader, M., Citron, M., Loetscher, H., Jacobsen, H. and Haass, C. (1999), Biochemistry 38, 14600-5.

Alpha-synuclein immunoreactive Lewy bodies and Lewy neurites in Parkinson's disease are detectable by an advanced silver-staining technique.

Sandmann-Keil, D., Braak, H., Okochi, M., Haass, C. and Braak, E. (1999), Acta Neuropathol (Berl) 98, 461-4.

The presenilins in Alzheimer's disease--proteolysis holds the key.

Haass, C. and De Strooper, B. (1999), Science 286, 916-9.

Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide production and requires a critical aspartate residue for its function in amyloidogenesis.

Leimer, U., Lun, K., Romig, H., Walter, J., Grunberg, J., Brand, M. and Haass, C. (1999), Biochemistry 38, 13602-9.

A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling.

Steiner, H., Duff, K., Capell, A., Romig, H., Grim, M.G., Lincoln, S., Hardy, J., Yu, X., Picciano, M., Fechteler, K., Citron, M., Kopan, R., Pesold, B., Keck, S., Baader, M., Tomita, T., Iwatsubo, T., Baumeister, R. and Haass, C. (1999), J Biol Chem 274, 28669-73.

hFE65L influences amyloid precursor protein maturation and secretion.

Guenette, S.Y., Chen, J., Ferland, A., Haass, C., Capell, A. and Tanzi, R.E. (1999), J Neurochem 73, 985-93.

Proteolysis by presenilins and the renaissance of tau.

Haass, C. and Mandelkow, E. (1999), Trends Cell Biol 9, 241-4.

Cholesterol-dependent generation of a seeding amyloid beta-protein in cell culture.

Mizuno, T., Nakata, M., Naiki, H., Michikawa, M., Wang, R., Haass, C. and Yanagisawa, K. (1999), J Biol Chem 274, 15110-4.

Apoptosis. Dead end for neurodegeneration?

Haass, C. (1999), Nature 399, 204-5, 207.

Analysis of presenilin 1 and presenilin 2 expression and processing by newly developed monoclonal antibodies.

Diehlmann, A., Ida, N., Weggen, S., Grunberg, J., Haass, C., Masters, C.L., Bayer, T.A. and Beyreuther, K. (1999), J Neurosci Res 56, 405-19.

Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease.

Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C. and Fahrenholz, F. (1999), Proc Natl Acad Sci U S A 96, 3922-7.

The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing.

Steiner, H., Romig, H., Grim, M.G., Philipp, U., Pesold, B., Citron, M., Baumeister, R. and Haass, C. (1999), J Biol Chem 274, 7615-8.

Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis.

Walter, J., Schindzielorz, A., Grunberg, J. and Haass, C. (1999), Proc Natl Acad Sci U S A 96, 1391-6.

Fleecy amyloid deposits in the internal layers of the human entorhinal cortex are comprised of N-terminal truncated fragments of Abeta.

Thal, D.R., Sassin, I., Schultz, C., Haass, C., Braak, E. and Braak, H. (1999), J Neuropathol Exp Neurol 58, 210-6.

Proteolytic processing and degradation of Alzheimer's disease relevant proteins.

Steiner, H., Capell, A. and Haass, C. (1999), Biochem Soc Trans 27, 234-42.

Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease.

Steiner, H., Capell, A., Leimer, U. and Haass, C. (1999), Eur Arch Psychiatry Clin Neurosci 249, 266-70.

The biological and pathological function of presenilin proteins—simple cell systems and a worm in Alzheimer's disease research.

Haass, C. and Baumeister, R. (1999), Eur Arch Psychiatry Clin Neurosci 249 Suppl 3, 23-7.

Biology of Alzheimer's disease.

Haass, C. (1999), Eur Arch Psychiatry Clin Neurosci 249, 265

Expression of Alzheimer's disease-associated presenilin-1 is controlled by proteolytic degradation and complex formation.

Steiner, H., Capell, A., Pesold, B., Citron, M., Kloetzel, P.M., Selkoe, D.J., Romig, H., Mendla, K. and Haass, C. (1998), J Biol Chem 273, 32322-31.

Truncated presenilin 2 derived from differentially spliced mRNA does not affect the ratio of amyloid beta-peptide 1-42/1-40.

Grunberg, J., Walter, J., Eckman, C., Capell, A., Schindzielorz, A., Younkin, S., Mehta, N., Hardy, J. and Haass, C. (1998), Neuroreport 9, 3293-9.

Cholesterol-dependent generation of a unique amyloid beta-protein from apically missorted amyloid precursor protein in MDCK cells.

Mizuno, T., Haass, C., Michikawa, M. and Yanagisawa, K. (1998), Biochim Biophys Acta 1373, 119-30.

Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain.

Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T.C., Iwatsubo, T., Capell, A., Walter, J., Grunberg, J., Ueyama, Y., Haass, C. and Ihara, Y. (1998), J Neurochem 71, 313-22.

Caspase-mediated cleavage is not required for the activity of presenilins in amyloidogenesis and NOTCH signaling.

Brockhaus, M., Grunberg, J., Rohrig, S., Loetscher, H., Wittenburg, N., Baumeister, R., Jacobsen, H. and Haass, C. (1998), Neuroreport 9, 1481-6.

Proteolytic fragments of the Alzheimer's disease associated presenilins-1 and -2 are phosphorylated in vivo by distinct cellular mechanisms.

Walter, J., Grunberg, J., Schindzielorz, A. and Haass, C. (1998), Biochemistry 37, 5961-7.

Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family.

Grunberg, J., Walter, J., Loetscher, H., Deuschle, U., Jacobsen, H. and Haass, C. (1998), Biochemistry 37, 2263-70.

The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex.

Capell, A., Grunberg, J., Pesold, B., Diehlmann, A., Citron, M., Nixon, R., Beyreuther, K., Selkoe, D.J. and Haass, C. (1998), J Biol Chem 273, 3205-11.

Alzheimer's disease. A technical KO of amyloid-beta peptide.

Haass, C. and Selkoe, D.J. (1998), Nature 391, 339-40.

Proteolytic processing of Alzheimer's disease associated proteins.

Haass, C., Grunberg, J., Capell, A., Wild-Bode, C., Leimer, U., Walter, J., Yamazaki, T., Ihara, I.,
Zweckbronner, I., Jakubek, C. and Baumeister, R. (1998), J Neural Transm Suppl 53, 159-67.

What do we learn from a few familial Alzheimer's disease cases?

Haass, C. and Baumeister, R. (1998), J Neural Transm Suppl 54, 137-45.

Cellular expression and proteolytic processing of presenilin proteins is developmentally regulated during neuronal differentiation.

Capell, A., Saffrich, R., Olivo, J.C., Meyn, L., Walter, J., Grunberg, J., Mathews, P., Nixon, R., Dotti, C. and Haass, C. (1997), J Neurochem 69, 2432-40.

Enhanced release of secreted form of Alzheimer's amyloid precursor protein from PC12 cells by nicotine.

Kim, S.H., Kim, Y.K., Jeong, S.J., Haass, C., Kim, Y.H. and Suh, Y.H. (1997), Mol Pharmacol 52, 430-6.

Presenilins are processed by caspase-type proteases.

Loetscher, H., Deuschle, U., Brockhaus, M., Reinhardt, D., Nelboeck, P., Mous, J., Grunberg, J., Haass, C. and Jacobsen, H. (1997), J Biol Chem 272, 20655-9.

Specific increase in amyloid beta-protein 42 secretion ratio by calpain inhibition.

Yamazaki, T., Haass, C., Saido, T.C., Omura, S. and Ihara, Y. (1997), Biochemistry 36, 8377-83.

Intracellular generation and accumulation of amyloid beta-peptide terminating at amino acid 42.

Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y. and Haass, C. (1997), J Biol Chem 272, 16085-8.

Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C.

Walter, J., Grunberg, J., Capell, A., Pesold, B., Schindzielorz, A., Citron, M., Mendla, K., George-Hyslop, P.S., Multhaup, G., Selkoe, D.J. and Haass, C. (1997), Proc Natl Acad Sci U S A 94, 5349-54.

Presenilins: genes for life and death.

Haass, C. (1997), Neuron 18, 687-90.

Human presenilin-1, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing.

Baumeister, R., Leimer, U., Zweckbronner, I., Jakubek, C., Grunberg, J. and Haass, C. (1997), Genes Funct 1, 149-59.

Enhanced production and oligomerization of the 42-residue amyloid beta-protein by Chinese hamster ovary cells stably expressing mutant presenilins.

Xia, W., Zhang, J., Kholodenko, D., Citron, M., Podlisny, M.B., Teplow, D.B., Haass, C., Seubert, P., Koo, E.H. and Selkoe, D.J. (1997), J Biol Chem 272, 7977-82.

The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue.

Tomita, T., Maruyama, K., Saido, T.C., Kume, H., Shinozaki, K., Tokuhiro, S., Capell, A., Walter, J., Grunberg, J., Haass, C., Iwatsubo, T. and Obata, K. (1997), Proc Natl Acad Sci U S A 94, 2025-30.

Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.

Walter, J., Capell, A., Hung, A.Y., Langen, H., Schnolzer, M., Thinakaran, G., Sisodia, S.S., Selkoe, D.J. and Haass, C. (1997), J Biol Chem 272, 1896-903.

Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue.

Podlisny, M.B., Citron, M., Amarante, P., Sherrington, R., Xia, W., Zhang, J., Diehl, T., Levesque, G., Fraser, P., Haass, C., Koo, E.H., Seubert, P., St George-Hyslop, P., Teplow, D.B. and Selkoe, D.J. (1997), Neurobiol Dis 3, 325-37.

The Alzheimer's disease-associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum.

Walter, J., Capell, A., Grunberg, J., Pesold, B., Schindzielorz, A., Prior, R., Podlisny, M.B., Fraser, P., Hyslop, P.S., Selkoe, D.J. and Haass, C. (1996), Mol Med 2, 673-91.

Presenile because of presenilin: the presenilin genes and early onset Alzheimer's disease.

Haass, C. (1996), Curr Opin Neurol 9, 254-9.

Inhibition of amyloid beta-protein production in neural cells by the serine protease inhibitor AEBSF.

Citron, M., Diehl, T.S., Capell, A., Haass, C., Teplow, D.B. and Selkoe, D.J. (1996), Neuron 17, 171-9.

Degradation of amyloid beta-protein by a serine protease-alpha2-macroglobulin complex.

Qiu, W.Q., Borth, W., Ye, Z., Haass, C., Teplow, D.B. and Selkoe, D.J. (1996), J Biol Chem 271, 8443-51.

The role of APP processing and trafficking pathways in the formation of amyloid beta-protein.

Selkoe, D.J., Yamazaki, T., Citron, M., Podlisny, M.B., Koo, E.H., Teplow, D.B. and Haass, C. (1996), Ann N Y
Acad Sci 777, 57-64.

The molecular significance of amyloid beta-peptide for Alzheimer's disease.

Haass, C. (1996), Eur Arch Psychiatry Clin Neurosci 246, 118-23.

The Swedish mutation causes early-onset Alzheimer's disease by beta-secretase cleavage within the secretory pathway.

Haass, C., Lemere, C.A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L. and Selkoe, D.J. (1995), Nat Med 1, 1291-6.

Lysosomal processing of amyloid precursor protein to A beta peptides: a distinct role for cathepsin S.

Munger, J.S., Haass, C., Lemere, C.A., Shi, G.P., Wong, W.S., Teplow, D.B., Selkoe, D.J. and Chapman, H.A. (1995), Biochem J 311 ( Pt 1), 299-305.

The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study.

Lemere, C.A., Munger, J.S., Shi, G.P., Natkin, L., Haass, C., Chapman, H.A. and Selkoe, D.J. (1995), Am J Pathol 146, 848-60.

The vacuolar H(+)-ATPase inhibitor bafilomycin A1 differentially affects proteolytic processing of mutant and wild-type beta-amyloid precursor protein.

Haass, C., Capell, A., Citron, M., Teplow, D.B. and Selkoe, D.J. (1995), J Biol Chem 270, 6186-92.

Polarized sorting of beta-amyloid precursor protein and its proteolytic products in MDCK cells is regulated by two independent signals.

Haass, C., Koo, E.H., Capell, A., Teplow, D.B. and Selkoe, D.J. (1995), J Cell Biol 128, 537-47.

Metabolism of the "Swedish" amyloid precursor protein variant in Madin-Darby canine kidney cells.

Lo, A.C., Haass, C., Wagner, S.L., Teplow, D.B. and Sisodia, S.S. (1994), J Biol Chem 269, 30966-73.

Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid beta-protein precursor.

Haass, C., Hung, A.Y., Selkoe, D.J. and Teplow, D.B. (1994), J Biol Chem 269, 17741-8.

Polarized secretion of beta-amyloid precursor protein and amyloid beta-peptide in MDCK cells.

Haass, C., Koo, E.H., Teplow, D.B. and Selkoe, D.J. (1994), Proc Natl Acad Sci U S A 91, 1564-8.

Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide.

Haass, C. and Selkoe, D.J. (1993), Cell 75, 1039-42.

Activation of protein kinase C inhibits cellular production of the amyloid beta-protein.

Hung, A.Y., Haass, C., Nitsch, R.M., Qiu, W.Q., Citron, M., Wurtman, R.J., Growdon, J.H. and Selkoe, D.J. (1993), J Biol Chem 268, 22959-62.

Production of amyloid-beta-peptide by cultured cells: no evidence for internal initiation of translation at Met596.

Citron, M., Haass, C. and Selkoe, D.J. (1993), Neurobiol Aging 14, 571-3.

Normal cellular processing of the beta-amyloid precursor protein results in the secretion of the amyloid beta peptide and related molecules.

Haass, C., Hung, A.Y., Schlossmacher, M.G., Oltersdorf, T., Teplow, D.B. and Selkoe, D.J. (1993), Ann N Y Acad Sci 695, 109-16.

beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.

Haass, C., Hung, A.Y., Schlossmacher, M.G., Teplow, D.B. and Selkoe, D.J. (1993), J Biol Chem 268, 3021-4.

Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.

Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A.Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I. and Selkoe, D.J. (1992), Nature 360, 672-4.

Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.

Hung, A.Y., Koo, E.H., Haass, C. and Selkoe, D.J. (1992), Proc Natl Acad Sci U S A 89, 9439-43.

Amyloid beta-peptide is produced by cultured cells during normal metabolism.

Haass, C., Schlossmacher, M.G., Hung, A.Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B.L., Lieberburg, I., Koo, E.H., Schenk, D., Teplow, D.B. and et, a.l. (1992), Nature 359, 322-5.

Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments.

Haass, C., Koo, E.H., Mellon, A., Hung, A.Y. and Selkoe, D.J. (1992), Nature 357, 500-3.

Molecular characterization of the genomic regions of the Drosophila alpha-type subunit proteasome genes PROS-Dm28.1 and PROS-Dm35.

Frentzel, S., Troxell, M., Haass, C., Pesold-Hurt, B., Glatzer, K.H. and Kloetzel, P.M. (1992), Eur J Biochem 205, 1043-51.

Detection of distinct isoform patterns of the beta-amyloid precursor protein in human platelets and lymphocytes.

Schlossmacher, M.G., Ostaszewski, B.L., Hecker, L.I., Celi, A., Haass, C., Chin, D., Lieberburg, I., Furie, B.C., Furie, B. and Selkoe, D.J. (1992), Neurobiol Aging 13, 421-34.

Processing of beta-amyloid precursor protein in microglia andastrocytes favors an internal localization over constitutive secretion.

Haass, C., Hung, A.Y. and Selkoe, D.J. (1991), J Neurosci 11, 3783-93.

The proteasome of Drosophila and features of the evolutionarily conserved PROS-gene family.

Kloetzel, P.M., Frentzel, S., Gernold, M., Haass, C., Klein, U., Pesold-Hurt, B. and Seelig, A. (1991), Biomed Biochim Acta 50, 451-7.

The Drosophila PROS-29 gene is a new member of the PROS-gene family.

Haass, C., Pesold-Hurt, B. and Kloetzel, P.M. (1990), Nucleic Acids Res 18, 4018

Developmental expression of Drosophila melanogaster small heat-shock proteins.

Haass, C., Klein, U. and Kloetzel, P.M. (1990), J Cell Sci 96 ( Pt 3), 413-8.

The Drosophila PROS-28.1 gene is a member of the proteasome gene family.

Haass, C., Pesold-Hurt, B., Multhaup, G., Beyreuther, K. and Kloetzel, P.M. (1990), Gene 90, 235-41.

Molecular analysis of alpha ecdysone induced 16S complexes in Drosophila Schneider's S3 cells.

Haass, C. and Kloetzel, P.M. (1990), Biochem Biophys Res Commun 168, 314-9.

The PROS-35 gene encodes the 35 kd protein subunit of Drosophila melanogaster proteasome.

Haass, C., Pesold-Hurt, B., Multhaup, G., Beyreuther, K. and Kloetzel, P.M. (1989), EMBO J 8, 2373-9.

The Drosophila proteasome undergoes changes in its subunit pattern during development.

Haass, C. and Kloetzel, P.M. (1989, Exp Cell Res 180, 243-52.

Drosophila small cytoplasmic 19S ribonucleoprotein is homologous to the rat multicatalytic proteinase.

Falkenburg, P.E., Haass, C., Kloetzel, P.M., Niedel, B., Kopp, F., Kuehn, L. and Dahlmann, B. (1988), Nature 331, 190-2.


Forschungsschwerpunkte

In meinem Labor konzentrieren wir uns auf die zellulären Mechanismen der Neurodegeneration. Wir glauben, dass Proteinablagerung und Oligomerisierung von amyloiden Peptiden durch gemeinsame Mechanismen herbeigeführt werden.
Unser Fokus liegt auf folgenden neurodegenerativen Erkrankungen:

  • Alzheimer Erkrankung (AD) mit einem speziellen Fokus auf der regulierten Intramembranproteolyse (RIP)
  • Parkinson Erkrankung (PD)
  • Frontotemporale Degeneration (FTD)
  • Amyotrophe Laterale Sclerose (ALS)
Abb. 1. Proteinablagerung als ein gemeinsames Merkmal verschiedener neurodegenerativer Erkrankungen.
Abb. 1. Proteinablagerung als ein gemeinsames Merkmal verschiedener neurodegenerativer Erkrankungen.Zum Vergrößern bitte auf die Lupe klicken.

Mein Interesse auf dem Gebiet der Alzheimer Erkrankung wurde 1992 geweckt, als ich eine sehr überraschende und überaus unerwartete Beobachtung machte, nämlich dass das Amyloid β Peptid (Aβ), der wichtigste Bestandteil Alzheimer typischer Plaques, lebenslang produziert wird.
Diese Entdeckung änderte die allgemeine Auffassung von Alzheimer und heute ist klar, dass Alzheimer ein Teil des normalen Alterungsprozesses ist. Weil Aβ eine zentrale Rolle in der Alzheimer-Symptomatik spielt, untersuchen wir den zellulären Mechanismus der hinter seiner Produktion steckt.
Es wurde schnell klar, dass Aβ durch einen proteolytischen Prozess erzeugt wird, der von zwei Proteasen gesteuert wird: β-, und γ-Sekretase (Abb. 2) Sezerniertes Aβ aggregiert und bildet kleine lösliche Oligomere, von denen man annimmt, dass sie neurotoxisch sind, während die Plaques selbst wohl eher harmlos sind. (Abb. 2).

Abb. 2: Proteolytische Bildung von Amyloid β-Peptid und γ-Sekretase.
Abb. 2: Proteolytische Bildung von Amyloid β-Peptid und γ-Sekretase.Zum Vergrößern bitte auf die Lupe klicken.

Beide Sekretasen sind Zielmoleküle der Pharmaindustrie, da Ihre Inhibierung die altersbezogene Neuropathologie verlangsamt, die durch Aggregation von Aβ verursacht wird. Unsere Arbeit auf dem Gebiet der γ-Sekretase (in Zusammenarbeit mit Herrn Prof. Dr. Harald Steiner) konzentriert sich auf deren Identifizierung, Funktion, Assemblierung, Rekonstitution, Modulation und Inhibition. Zusammen mit Dr. Regina Fluhrer erforschen wir die generellen Mechanismen der intramembranösen Proteolyse. Gleichzeitig studieren wir die Funktion und Regulierung der β-Sekretase (BACE1), wobei wir insbesondere an den regulativen Mechanismen interessiert sind, welche vielleicht für die gesteigerte β-Sekretase Aktivität während des Alterungsprozesses verantwortlich sind. Wir konnten zeigen, dass die β-Sekretase funktionell für die Myelinisierung von Axonen des peripheren Nervensystems nötig ist (Abb. 3). Ein weiterer Forschungsschwerpunkt ist die Regulation der γ-Secretase, da ihre verstärkte Aktivität die Alzheimer Pathologie verhindern könnte.

Abb.3: Knock-out der β-Sekretase führt zu Hypomyelinisierung.
Abb.3: Knock-out der β-Sekretase führt zu Hypomyelinisierung.Zum Vergrößern bitte auf die Lupe klicken.

Unsere FTD und ALS Forschung konzentriert sich auf Tau, TDP-43, FUS und Progranulin. Wiederum sind wir spezifisch an den biologischen Mechanismen interessiert, die durch krankheitsassoziierte Mutationen in diesen Genen hervorgerufen werden. Kürzlich konnten wir zeigen, dass FUS-assoziierte Mutationen den Transport in den Zellkern beeinträchtigen (Abb. 4). Darüber hinaus fanden wir, dass der Grad der zellulären Fehllokalisation negativ mit dem Alter des Ausbruchs von ALS korreliert.

Abb. 4: Eine ALS assoziierte FUS Mutation verursacht dessen cytoplasmatische Fehllokalisation. © The EMBO Journal (2010) 29, 2841 - 2857 | doi:10.1038/emboj.2010.143
Abb. 4: Eine ALS assoziierte FUS Mutation verursacht dessen cytoplasmatische Fehllokalisation. © The EMBO Journal (2010) 29, 2841 - 2857 | doi:10.1038/emboj.2010.143Zum Vergrößern bitte auf die Lupe klicken.

In ähnlicher Weise konzentriert sich unsere Parkinson Forschung an den genetisch assoziierten Genen  α-synuclein, parkin, Pink-1 und DJ-1. Hier konnten wir kürzlich zeigen, dass erhöhte Mengen von α-synuclein die mitochondriale Fusion inhibieren, ein Prozess, welcher von Pink-1, parking und DJ-1 rückgängig gemacht werden kann. Die Parkinsonforschung wird zusammen mit Frau Dr. Winklhofer durchgeführt.

Zebrafische (Abb. 5) werden genutzt, um die biologischen Funktionen und Fehlfunktionen von Genen zu untersuchen, die mit Neurodegeneration in Verbindung gebracht werden.  Dieses Projekt wird in Zusammenarbeit mit Frau Dr. Bettina Schmid durchgeführt, die am Standort München die DZNE Core Facility Fischhaltung leitet.

Die Homepage des Kooperationspartners finden sie hier.

Abb.5: ein Tau transgener Zebrafisch
Abb.5: ein Tau transgener ZebrafischZum Vergrößern bitte auf die Lupe klicken.

General reading

Initiation and propagation of neurodegeneration

Haas C. (2010), Nature Medicine. 16, 1201-04.

Alzheimer – Mechanismen und therapeutische Ansätze. Warum wir im Alter dement werden

Haass C. (2009), Biologie in unserer Zeit. 39, 92–100. 

The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases.

Winklhofer KF, Tatzelt J, Haass, C. (2008), EMBO J. 27, 336-349.

Intramembrane proteolysis by gamma-secretase.

Steiner H, Fluhrer R, Haass C. (2008), J. Biol. Chem. 283, 29627 - 31.

Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.

Haass C, Selkoe DJ. (2007), Nat Rev Mol Cell Biol 8, 101-12.

Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation.

Haass C. (2004), EMBO J 23, 483-8.

Games played by rogue proteins in prion disorders and Alzheimer's disease.

Aguzzi A, Haass C. (2003), Science 302, 814-8.