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Molecular pathogenesis of Parkinson disease: insights from genetic studies

Published online by Cambridge University Press:  27 July 2009

Thomas Gasser
Thomas Gasser
Affiliation:
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler Str. 3, 72076 Tübingen, Germany. Tel: +49 7071 29 86529; Fax: +49 7071 29 4839; E-mail: thomas.gasser@med.uni-tuebingen.de
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Abstract

Over the past few years, genetic findings have changed our views on the molecular pathogenesis of Parkinson disease (PD), as mutations in a growing number of genes have been found to cause monogenic forms of the disorder. These mutations cause neuronal dysfunction and neurodegeneration either by a toxic gain of function, as in the case of the dominant forms of monogenic PD caused by mutations in the genes for α-synuclein or LRRK2, or by a loss of an intrinsic protective function, as is likely for the recessive PD genes parkin (PRKN), PINK1 and DJ-1. Evidence is emerging that at least some of the pathways uncovered in the rare monogenic forms of PD may play a direct role in the aetiology of the common sporadic disorder and that variants of the respective genes contribute to the risk of developing the disease. These findings will allow the search for new treatment strategies that focus on the underlying molecular pathophysiology, rather than simply on ameliorating symptoms.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e22
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

The Michael J. Fox Foundation is a private organisation funding and supporting Parkinson disease research: http://www.michaeljfox.org/

The PD-Gene database aims to provide an unbiased, centralised, publicly available and regularly updated collection of genetic association studies in Parkinson disease: http://www.pdgene.org

The European Parkinson's Disease Association (EPDA) is a concerned with the health and welfare of people living with Parkinson disease and their families and carers: http://www.epda.eu.com/

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Healy, D.G. et al. (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurology 7, 583-590CrossRefGoogle ScholarPubMed
Gupta, A., Dawson, V.L. and Dawson, T.M. (2008) What causes cell death in Parkinson's disease? Annals of Neurology 64 Suppl 2, S3-15Google Scholar
Hardy, J. (2005) Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: ‘permissive templating’ as a general mechanism underlying neurodegeneration. Biochemical Society Transactions 33, 578-581CrossRefGoogle ScholarPubMed