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Molecular pathogenesis of Parkinson disease: insights from genetic studies

  • Thomas Gasser (a1)
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.

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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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