Prof. Dr. Donato A. Di Monte

Deputy of the Scientific Director and Group Leader

German Center for Neurodegenerative Diseases (DZNE)
Sigmund-Freud-Str. 27
53127 Bonn

+49 (0) 228 / 43302-650
+49 (0) 228 / 43302-538 (Secretary)

Group members

Name Telefon
Almana Mukabenova, Assistant +49 (0) 228 / 43302-538
Dr. Michael Helwig, Postdoc +49 (0) 228 / 43302-668
Dr. Ayse Ulusoy, Postdoc +49 (0) 228 / 43302-668
Dr. Blanca Perez-Revuelta, Postdoc +49 (0) 228 / 43302-668
Dr. Bettina Winzen-Reichert, Postdoc +49 (0) 228 / 43302-668
Dr. Ruth Musgrove, Postdoc +49 (0) 228 / 43302-668
Dr. Raffaella Rusconi, Postdoc +49 (0) 228 / 43302-668
Dr. Michael Klinkenberg, Postdoc +49 (0) 228 / 43302-668
Dr. Alison McCormack, Consultant +49 (0) 228 / 43302-668
Franziska Hesse, Technical Assistant +49 (0) 228 / 43302-668

Selected publications

Brain propagation of transduced α-synuclein involves non-fibrillar protein species and is enhanced in α-synuclein null mice.

Helwig M, Klinkenberg M, Rusconi R, Musgrove RE, Majbour NK, El-Agnaf OMA, Ulusoy A, Di Monte DA (2015) Brain, in press.           

Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease.

Tate CC, Chou VP, Campos C, Moalem AS, Di Monte DA, McGrogan M, Case CC, Manning-Bog AB (2015) J Tissue Eng Regen Med, in press.

Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury.

Ulusoy A, Musgrove RE, Rusconi R, Klinkenberg M, Helwig M, Schneider A, Di Monte DA (2015) Acta Neuropathol Commun 3, 13.

Function and developmental origin of a mesocortical inhibitory circuit.

Kabanova A, Pabst M, Lorkowski M, Braganza O, Boehlen A, Nikbakht N, Pothmann L, Vaswani AR, Musgrove R, Di Monte DA, Sauvage M, Beck H, Blaess S (2015) Nat Neurosci, 18, 872-882.

Metformin lowers Ser-129 phosphorylated α-synuclein levels via mTOR-dependent protein phosphatase 2A activation.

Pérez-Revuelta BI, Hettich MM, Ciociaro A, Rotermund C, Kahle PJ, Krauss S, Di Monte DA (2014) Cell Death Dis 5, e1209. 

Neurodegeneration by activation of the microglial complement-phagosome pathway.

Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA, Balling R, Neumann H (2014) J Neurosci 34, 8546-8556.          

Caudo-rostral brain spreading of α-synuclein through vagal connections.

Ulusoy A, Rusconi R, Pérez-Revuelta BI, Musgrove RE, Helwig M, Winzen-Reichert B, Di Monte DA (2013) EMBO Mol Med 5, 1051-1059.

α-Synuclein elevation in human neurodegenerative diseases: experimental, pathogenetic, and therapeutic implications.

Ulusoy A, Di Monte DA (2013) Mol Neurobiol 47, 484-494.

Increased α-synuclein phosphorylation and nitration in the aging primate substantia nigra.

McCormack AL, Mak SK, Di Monte DA (2012) Cell Death Dis 3, e315.

Restorative Effects of Platelet Derived Growth Factor-BB in Rodent Models of Parkinson's Disease.

Zachrisson O, Zhao M, Andersson A, Dannaeus K, Häggblad J, Isacson R, Nielsen E, Patrone C, Rönnholm H, Wikstrom L, Delfani K, McCormack AL, Palmer T, Di Monte DA, Hill MP, Janson-Lang AM, Haegerstrand A (2011) J Parkinsons Dis 1, 49-63.

α-Synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA (2010) PLoS One 5, e12122.

Lysosomal degradation of α-synuclein in vivo.

Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA (2010) J Biol Chem 285, 13621-13629.

Serine 129 phosphorylation reduces α-synuclein’s ability to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo.

Lou H, Montoya SE, Alerte TN, Wang J, Peng XM, Hong CS, Friedrich EE, Mader SA, Pedersen CJ, Marcus BS, McCormack AL, Di Monte DA, Daubner SC, Perez RG (2010) J Biol Ckem 285, 17648-17661.

Methionine oxidation stabilizes non-toxic oligomers of α-synuclein through strengthening the auto-inhibitory intra-molecular long-range interactions.

Zhou W, Long C, Reaney SH, Di Monte DA, Fink AL, Uversky VN (2010) Biochim Biophys Acta 1802, 322-330.

Decreased α-synuclein expression in the aging mouse substantia nigra.

Mak SK, McCormack AL, Langston JW, Kordower JH, Di Monte DA (2009) Exp Neurol 220, 359-365.

Enhanced α-synuclein expression in human neurodegenerative diseases: pathogenetic and therapeutic implications.

McCormack AL, Di Monte DA (2009) Curr Protein Pept Sci 10, 476-482.

Pathological modifications of α-synuclein in MPTP-treated squirrel monkeys.

McCormack AL, Mak SK, Shenasa M, Langston WJ, Forno LS, Di Monte DA (2008) J Neuropath Exp Neurol 67, 793-802.

Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease.

Hu X, Zhang D, Pang H, Caudle WM, Li Y, Gao H, Liu Y, Qian L, Wilson B, Di Monte DA, Ali SF, Zhang J, Block ML, Hong JS (2008) J Immunol 181, 7194-7204.

Paraquat exposure reduces nicotinic receptor-evoked dopamine release in monkey striatum.

O’Leary KT, Parameswaran N, Johnston LC, McIntosh JM, Di Monte DA, Quik M (2008) J Pharmacol Exp Ther 327, 124-129.

MAO-B elevation in mouse brain astrocytes results in Parkinson’s pathology.

Mallajosyula JK, Kaur D, Chinta SJ, Rajagopalan S, Rane A, Nicholls DG, Di Monte DA, Macarthur H, Andersen JK (2008) PLoS ONE 3, e1616.

Paraquat neurotoxicity is mediated by a Bak-dependent mechanism.

Fei Q, McCormack AL, Di Monte DA, Ethell DW (2008) J Biol Chem 283, 3357-3364.

Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter.

Manning-Bog AB, Perez XA, Reaney SH, Paletzki R, Isla MZ, Chou V, McCormack AL, Miller GW, Langston JW, Gerfen CR, Di Monte DA (2007) Neurobiol Dis 27, 141-150.

Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys.

Quik M, Cox H, Parameswaran N, O’Leary K, Langston JW, Di Monte DA (2007) Ann Neurol 62, 599-596.

Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration.

Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, Colebrooke RE, Di Monte DA, Emson PC, Miller GW (2007) J Neurosci 27, 8138-8148.

Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration.

Purisai MG, McCormack AL, Cumine S, Li J, Isla MZ, Di Monte DA (2007) Neurobiol Dis 25, 392-400.

Effect of 4-hydroxy-2-nonenal modification on α-synuclein aggregation.

Qin Z, Hu D, Han S, Reaney SH, Di Monte DA, Fink AL (2007) J Biol Chem 282, 5862-5870.

Increased murine neonatal iron intake results in parkinson-like neurodegeneration with age.

Kaur D, Peng J, Chinta SJ, Rajagopalan S, Di Monte DA, Cherny RA, Andersen JK (2007) Neurobiol Aging 28, 907-913.

Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration.

Peng J, Xie L, Stevenson FF, Melov S, Di Monte DA, Andersen J.K. (2006) J Neurosci 26, 11644-11651.

Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates.

Quik M, Parameswaran N, McCallum SE, Bordia T, Bao S, Mc Cormack A, Kim A, Tyndale RF, Langston JW, Di Monte DA (2006) J Neurochem 98, 1866-1875.

Lack of nigrostriatal pathology in a rat model of proteasome inhibition.

Manning-Bog AB, Reaney SH, Chou VP, Johnston LC, McCormack AL, Johnston J, Langston JW, Di Monte DA (2006) Ann Neurol 60, 256-260.

Curriculum Vitae

Prof. Di Monte received his Doctorate of Medicine and his residency training in Internal Medicine from the University of Bari, Italy. He completed post-doctoral research training in Biochemistry and Toxicology at the Karolinska Institute in Stockholm, Sweden, and at the School of Public Health, University of California, Berkeley. Prof. Di Monte then became an independent investigator at the Parkinson’s Institute (Sunnyvale, California) and was Director of the Institute’s Basic Research Department. He developed a successful line of research sponsored by the National Institutes of Health and other governmental and private agencies. In 2010, he joined the German Center for Neurodegenerative Diseases (DZNE) in Bonn as a Professor and Senior Research Group Leader. He also acts as the Center’s Deputy Scientific Director.

Prof. Di Monte has served as a member of numerous study sections, project steering committees and scientific advisory boards. He has authored or co-authored more than 150 peer-reviewed scientific publications. A new therapeutic approach discovered by Prof. Di Monte and his collaborators (patent # US7,718,677 B2) is presently being tested in Parkinson’s disease patients for the treatment of L-dopa-induced dyskinesias.  

Areas of investigation/research focus

Figure: Dopaminergic neurons are highly susceptible to degeneration in Parkinson’s disease. The figure shows cell bodies and processes of cultured dopaminergic neurons.
Figure: Dopaminergic neurons are highly susceptible to degeneration in Parkinson’s disease. The figure shows cell bodies and processes of cultured dopaminergic neurons.Click on the magnifying glass for a large image.

The primary goal of our research team is to identify mechanisms of neuronal degeneration that could be targeted for the prevention and treatment of human neurodegenerative diseases. Although our research is mainly focused on Parkinson’s disease, we aim to study mechanisms (e.g. protein aggregation and inflammation) and risk factors (e.g. aging) that are shared between Parkinson’s and other neurodegenerative disorders. We believe that bridging different human diseases will help us understand what makes neurons vulnerable to degenerative processes and what can be done to counteract these pathologic events.

Current research focus
Using a variety of neurochemical, molecular biology and immunohistochemical techniques, Prof. Di Monte’s group is presently investigating research areas that include:

  • Mechanisms of α-synuclein pathology. α-Synuclein is a protein involved in pathogenetic processes in Parkinson’s disease and other human neurodegenerative disorders (e.g. dementia with Lewy bodies). Its toxicity, as investigated by our research team, may arise from or be enhanced by abnormal aggregation, toxicant-protein interactions and impairment of degradation. Of note, similar mechanisms could underlie β-amyloid pathology in Alzheimer’s disease.  
  • Environmental toxicants and aging as neurodegenerative disease risk factors. Aging is an unequivocal risk factor for human neurodegenerative diseases, and toxic exposures are likely to play an important role in the pathogenesis of Parkinson’s disease. Mechanisms by which these risk factors enhance neuronal vulnerability to degenerative processes include oxidative stress, neuroinflammation and α-synuclein abnormalities.    
  • Screening and evaluation of neuroprotective/neurorestorative agents. Disease-modifying interventions are urgently needed for Parkinson’s disease. New therapeutic strategies that are currently being tested in our laboratory include the inhibition of α-synuclein expression using RNA interference-based technology and the enhancement of protein degradation by autophagy inducers.
  • Development and validation of experimental models. The availability of experimental models that reproduce key disease features is critical for investigating mechanisms of neurodegeneration and testing new therapeutics. A variety of Parkinson’s disease models are presently used or are being developed in our laboratory. They include in vitro and in vivo administration of neurotoxicants (e.g. MPTP, paraquat or 6-hydroxydopamine) or transgenic manipulation of specific proteins (e.g., overexpression or knock-out of α-synuclein).