Prof. Dr. Donato A. Di Monte

Deputy of the Scientific Director and Group Leader

German Center for Neurodegenerative Diseases (DZNE)
Ludwig-Erhard-Allee 2
53175 Bonn

donato.dimonte(at)dzne.de
+49 (0) 228 / 43302-650

More information

Group Members Curriculum Vitae

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

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).

Publications

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.

Paraquat-induced neurodegeneration: A model of Parkinson’s disease risk factors.

Di Monte DA (2008), In:  Parkinson’s Disease: Molecular and Therapeutic Insights from Model Systems (eds.  R. Nass and S. Przedborki), pp. 207-217, Academic Press, New York.

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.

Nicotine partially protects against paraquat-induced nigrostriatal damage in mice: Link to α6β2* nAChRs.

Khwaja M, McCormack AL, McIntosh JM, Di Monte DA, Quik M (2007), J Neurochem 100, 180-190.

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.