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Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represent the opinions of the authors and are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology.

Etiology of Parkinson’s disease

From the University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, United Kingdom, and Institute of Neurology, University College London, United Kingdom.

Address correspondence and reprint requests to Prof. A. Schapira, University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK; e-mail: a.schapira{at}medsch.ucl.ac.uk

The etiology of Parkinson’s disease (PD) has long been thought to involve both genetic and environmental factors, but until recently there has been no direct evidence to support either one as a causative factor. However, in the past 8 years six different genes have been identified as causing familial PD. Together, they support the notion that common pathogenetic mechanisms exist across the etiologic spectrum of PD. Specifically, mutations in -synuclein, parkin, UCHL1, DJ1, PINK1, and LRRK2 cause PD, with a Mendelian pattern of inheritance. DJ1 and PINK1 are mitochondrial proteins and overexpression of -synuclein and parkin induce mitochondrial defects. These same proteins are involved in the response to oxidative stress and affect proteasomal function. In contrast, few environmental factors have been characterized. Nevertheless, those toxins that have been demonstrated to have the ability to cause nigrostriatal cell death appear to interact by interfering with mitochondrial function, inducing oxidative stress, and modifying proteasomal function. Therefore, common themes are beginning to emerge in the etiopathogenesis of PD. This bodes well for research focused on the development of treatments that will modify the course of PD.

Supported by research grants from the Medical Research Council UK, the Parkinson’s Disease Society, the Wellcome Trust, and the Kattan Trust.

Publication of this supplement was supported by an educational grant from Teva Neuroscience and Eisai, Inc.

Disclosure: The sponsor has provided the author with the following: an honorarium for his participation in this project, personal honoraria and grant support during his career. The author has been consulted on manganese litigation.

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