Dr. Frank Striggow

Group Leader

German Center for Neurodegenerative Diseases (DZNE)
House 65
Leipziger Str. 44
39120 Magdeburg

frank.striggow(at)dzne.de
+49 (0) 391 / 6117-224
+49 (0) 391 / 67-24532

More information

Group Members Curriculum Vitae

Areas of investigation/research focus

Within the Research Group Neurodegeneration and Intervention Strategies, we investigate the molecular and cellular mechanisms of acute and chronic neuronal cell death, the pathogenesis of different neurodegenerative diseases and their clinical manifestation, i.e. familial and sporadic forms of Alzheimer’s disease (fAD, sAD), frontotemporal lobar dementia (FTLD), vascular and/or ischemia-dependent neurodegenerative diseases, Parkinson’s disease (PD) und Huntington’s disease (HD). Based on this, we would like to identify new targets and better therapeutic options to fight the devastating consequences of neurodegenerative diseases of the human CNS. For example, we are focused on the tau protein, which is crucially involved in the pathogenesis of FTLD and (potentially) AD. Recently, we could show that soluble tau oligomers, instead of insoluble tau aggregates, induce synaptic damage and neuronal death (Hinners et al., Mol. Cell. Neurosci. 2008). Consistently, drugs able to prevent tau phosphorylation and hyperphosphorylation do also protect synapses, neurons and improve neurological deficits of diseased animals.

Click on the magnifying glass for a large image.
Fig. 1: The tau cascade – from Microtubule-associated protein to neurofibrillary tangles (NFTs) and neuronal dysfunction.
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Fig. 2:The tau kinase inhibitor SRN556 protects hippocampal synapses and prevents Alzheimer-type neurodegeneration. Reprinted from Mol Cell Neurosci, 37(3), Hinners I et al., Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation, 559-67, Copyright (2008), with permission from Elsevier.

In the BMBF-funded project IMAS (Project Coordinator: Dr. Till Mack), we and partners at University of Leipzig, Technical University of Ilmenau and the Fraunhofer Institute for Factory Operation and Automation develop an approach, that is suitable for the efficient screening and validation of drugs interfering with tau-mediated signaling cascades and pathologies. The IMAS platform relies on impedance-based spectroscopy and is able to handle cell or slice cultures.

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Fig. 3: Analysis of protein hyperphosporylation by impedance-based spectroscopy. Jahnke et al. Lab Chip, 2009, 9, 1422–28 - Reproduced by permission of The Royal Society of Chemistry dx.doi.org/10.1039/b819754g.

As partner institution within the excellence cluster „Spitzenforschung und Innovationen in den Neuen Ländern – Protein-Kompetenznetzwek Halle (ProNEt-T3) – Tools, Targets, Therapeutics“, we are going to design novel, multifunctional drug candidates for the treatment of neurodegenerative diseases. In particular, we are interested in specific immunophilin effectors to target neuroprotective, immune modulatory and/or regenerative signaling cascades in the brain. In this project, we continue our long-term collaboration with the Max Planck Research Unit for Enzymology of Protein Folding (Prof. Gunter Fischer) in Halle/Saale, Germany. Further partners are the Martin-Luther-University Halle-Wittenberg, the Technical University Munich and the German Leibniz Association.

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Fig. 4: The sprecific FKBP38 inhibitor DM-CHX stimulates the proliferation of endogenous stem cells (left, green flurescence) and their neuronal differentiation (right, yellow fluorescence) in the rat cortex after focal cerebral ischemia. This research was originally published in The Journal of Biological Chemistry. F. Edlich, et al. The specific FKBP38 inhibitor N-(N’,N’-dimethylcarboxamidomethyl)-cycloheximide has potent neuroprotective and neurotrophic properties in brain ischemia. J. Biol. Chem. 2006; 281:14961-70. © the American Society for Biochemistry and Molecular Biology.

Publications

Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle.

Gellerich FN, Gizatullina Z, Trumbekaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F. Biochem J. 2012 May 1;443(3):747-55.

Impedance spectroscopy based measurement system for quantitative and label-free real-time monitoring of tauopathy in hippocampal slice cultures.

HG Jahnke, A Braesigk, TG Mack, S Pönick, F Striggow, AA Robitzki; Biosens Bioelectron. 2012 Feb 15;32(1):250-8. Epub 2011 Dec 23.

Insufficient endogenous redox buffer capacity may underlie neuronal vulnerability to cerebral ischemia and reperfusion.

P Röhnert, UH Schröder, I Ziabreva, M Täger, KG Reymann, F Striggow; J Neurosci Res. 2012 Jan;90(1):193-202. doi: 10.1002/jnr.22754. Epub 2011 Oct 4.

Effects of cyclosporine A and its immunosuppressive or non-immunosuppressive derivatives [D-Ser]8-CsA and Cs9 on mitochondria from different brain regions.

Z. Gizatullina, T.M. Gaynutdinov, H. Svoboda, D.  Jerzembek, A. Knabe, S. Vielhaber, M. Malesevic, H.-J. Heinze, G. Fischer, F. Striggow and F.N. Gellerich: Mitochondrion 11, 421-429 (2011).

A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoring.

D. Krinke, H.G. Jahnke, T.G. Mack, A. Hirche, F. Striggow and A.A Robitzki: Biosens. Bioelectron.26, 162-168 (2010), Epub 2010 Jun 9.

The regulation of OXPHOS by extramitochondrial calcium.

F.N. Gellerich, Z. Gizatullina, S. Trumbeckaite, H.P. Nguyen, T. Pallas, O. Arandarcikaite, S. Vielhaber, E. Seppet and F. Striggow: Biochim. Biophys. Acta. 1797, 1018-1027 (2010), Epub 2010 Feb 6

Extramitochondrial Ca2+ in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand.

F.N. Gellerich,  Z. Gizatullina, O. Arandacikaite, D. Jerzembeck, S. Vielhaber, E. Seppet and F. Striggow: PloS one 4, e8181 (2009)

Mitochondria and energetic depression in cell pathophysiology.

E. Seppet, M. Gruno, A. Peetsalu, Z. Gizatullina, H.P. Nguyen, S. Vielhaber, M. Wussling, S. Trumbeckaite, O. Arandarcikaite, D. Jerzembeck, M. Sonnabend, K. Jegorov, F. Striggow and F.N. Gellerich: Int. J. Mol. Sci. 10, 2252-2303 (2009)

An impedimetric microelectrode-based array sensor for label-free detection of tau hyperphosphorylation in human cells.

H.-G. Jahnke, A. Rothermel, I. Sternberger, T.G.A. Mack, R.G. Kurz, O. Pänkea, F. Striggow and A.A. Robitzki: Lab Chip 9, 1422-1428 (2009)

Impaired regulation of brain mitochondria by extramitochondrial Ca2+ in transgenic Huntington Disease rats.

F.N. Gellerich, Z. Gizatullina, H.P. Nguyen, S. Trumbeckaite, S. Vielhaber, E. Seppet, S. Zierz, B. Landwehrmeyer, O. Ries, S. von Hoersten and F. Striggow: J. Biol. Chem. 283, 30715-30724 (2008)

Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation.

A. Hinners, A. Hill, U. Otto, A. Michalsky, T.G.A. Mack and F. Striggow: Mol. Cell. Neurosci.  37, 559-567 (2008)

Mitochondrial medicine: The central role of mitochondria in cell pathophysiology.

E. Seppet, Z. Gizatullina, S. Trumbeckaite, S. Zierz, F. Striggow and F.N. Gellerich: in MOLECULAR SYSTEM BIOENERGETIC ENERGY FOR LIFE  Hrsg  V.A. Saks  STM books Wiley-VCH GmbH & Co. (2007) 479-520

The specific FKBP38 inhibitor N-(N’,N’-dimethylcarboxamidomethyl)-cycloheximide has potent neuroprotective and neurotrophic properties in brain ischemia.

F. Edlich, M. Weiwad, D. Wildemann, F. Jarczowski, S. Kilka, M.-C. Moutty, G. Jahreis, C. Lücke, W. Schmidt, F. Striggow and G. Fischer: J. Biol. Chem. 281, 14961-14970 (2006)

Decreased stability of Huntington mitochondria against calcium in  R6/2 mouse muscle.

Z.Z. Gizatullina, K.S. Lindenberg, B.G. Landwehrmeyer, Y. Chen, C.M. Kosinski, P.Harjes, W. Schmidt, F. Striggow, S. Zierz, and F.N. Gellerich: Ann. Neurol. 59, 407-411(2006)

Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in rats.

P. Henrich-Noack, F. Striggow, G. Reiser and K.G. Reymann: J Neurosci Res. 83, 469-475 (2006)

Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation.

A. Bukowska, U. Lendeckel, D. Hirte, C. Wolke, F. Striggow, P. Röhnert, C. Huth, H.U. Klein, and A. Goette: Cell Mol Life Sci. 63, 333-342 (2006)

Hochdurchsatz-Screening und Wirkstoffentwicklung in Gewebekulturen.

P. Röhnert, T. Mack, F.N. Gellerich, F. Striggow, A. Hoffmann: Laborwelt 5, 39-41 (2005)

Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen-glucose-deprivation in organotypic hippocampal slice cultures.

M. Martínez-Sánchez, F. Striggow, U. Schroeder, S. Kahlert, K.G. Reymann and G. Reiser: Neurosci. 128, 729-740 (2004)

Automatisiertes funktionelles Screening in Gewebekulturen.

C. Heers, P. Röhnert, T. Mack and F. Striggow: Laborwelt 1, 2-4 (2004)

Short-term down-regulation of the brain-specific, PtdIns(3,4,5)P3/ Ins(1,3,4,5)P4-binding, adapter protein, p42IP4 / centaurin-a1 in rat brain after acoustic and electric stimulation.

G. Reiser, F. Striggow, C. Hackmann, H. Schwegler, D.M. Yilmazer-Hanke: Neurochem Int. 45, 89-93 (2004)

Influence of transient global ischemia on expression of prothrombin, PN-1 and protease-activated receptors.

M. Riek-Burchardt, F. Striggow, P. Henrich-Noack, G. Reiser, K.G. Reymann: Neurosci. Lett. 329, 181-184 (2002)

Telomics - tissue-based screening for target validation and preclinical drug development.

F. Striggow, P. Röhnert and K. G. Reymann: NewDrugs 1, 30-36 (2002)

Four different subtypes of protease-activated receptors are co-expressed in the CNS.

F. Striggow, M. Riek, A. Kiesel, W. Schmidt, P. Henrich-Noack, K.G. Reymann and G. Reiser, Eur. J. Neurosci. 14(4), 595-608 (2001)

Distinct Ca2+ thresholds determine cytochrome c release or permeability transition pore opening in brain mitochondria.

L. Schild, G. Keilhoff, W. Augustin, G. Reiser and F. Striggow: FASEB J. 15(3), 565-567 (2001)

The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations.

F. Striggow, M. Riek, J. Breder, P. Henrich-Noack, K.G. Reymann and G. Reiser: Proc. Natl. Acad. Sci. USA 97, 2264-2269 (2000)

FK506 acts highly neuroprotective in an in vivo model of global cerebral ischemia but not under in vitro conditions.

W. Schmidt, F. Striggow, G. Reiser and K. G. Reymann: In Immunophilins in the Brain; FKBP-Ligands: Novel strategies for the treatment of neurodegenerative disorders (eds. B. Gold, G. Fischer and T. Herdegen), Prous Science, S.A., Barcelona, Spain, 269-276 (2000)

Regulation of intracellular calcium release channel function by arachidonic acid and leukotriene B4.

F. Striggow and B. E. Ehrlich: Biochem. Biophys. Res. Commun. 237, 413-418 (1997)

Phorbol ester-induced shedding of intercellular adhesion molecule-1 (ICAM-1) on erythroleukemic K 562 cells.

S. Fritz, F. Striggow, D. Reinhold, T. Schlüter, P. Schönfeld, S. Ansorge and R. Bohnensack: Biochem. Biophys. Acta 1312, 255-261 (1996)

Ligand-gated calcium channels inside and out.

F. Striggow and B. E. Ehrlich: Curr. Opin. Cell Biol. 8, 490-495 (1996)

The inositol 1,4,5-trisphosphate receptor of cerebellum: Mn2+-permeability and regulation by cytosolic Mn2+.

F. Striggow and B. E. Ehrlich: J. Gen. Physiol. 108, 115-124 (1996)

Inositol (1,4,5)-trisphosphate activates receptor-mediated calcium entry by two different pathways in hepatocytes.

F. Striggow and R. Bohnensack: Eur. J. Biochem. 222, 229-234 (1994)

Functional characterization of mitochondrial oxidative phosphorylation in saponin-skinned human muscle fibers.

W.S. Kunz, A.V. Kuznetsov, W. Schulze, K. Eichhorn, L. Schild, F. Striggow, R. Bohnensack, S. Neuhof, H. Grasshoff, H.W. Neumann and F.N. Gellerich: Biochim. Biophys. Acta 1144, 46-53 (1993)

Verapamil and diltiazem inhibit receptor-operated calcium channels and intracellular calcium oscillations in rat hepatocytes.

F. Striggow and R. Bohnensack: FEBS Lett. 318, 341-344 (1993)