Pathogenesis of Parkinson's disease

Authors

  • Etienne C. Hirsch PhD,

    1. Université Pierre et Marie Curie–Paris 06, Centre de Recherche de l'Institut du Cerveau et de la Moëlle Épinière, Hôpital de la Salpêtrière, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche U975, Paris, France
    3. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7225, Paris, France
    Search for more papers by this author
  • Peter Jenner PhD, DSc, FRPharmS,

    1. Neurodegenerative Diseases Research Centre, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College, London, United Kingdom
    Search for more papers by this author
  • Serge Przedborski MD, PhD

    Corresponding author
    1. Department of Neurology, Department of Pathology and Cell Biology, and the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York
    • Université Pierre et Marie Curie–Paris 06, Centre de Recherche de l'Institut du Cerveau et de la Moëlle Épinière, Hôpital de la Salpêtrière, Paris, France
    Search for more papers by this author

  • Relevant conflicts of interest/financial disclosures: The authors are supported by grants from the National Institutes of Health (NS042269, NS064191, NS38370, NS070276, and NS072182 to S.P.), the U.S. Department of Defense (W81XWH-08-1-0522, W81XWH-08-1-0465, and W81XWH-09-1-0245 to S.P.), the Parkinson Disease Foundation, the Thomas Hartman Foundation For Parkinson's Research, Project A.L.S, the Wings-over-Wall Street/Muscular Dystrophy Association. INSERM, CNRS, Université Pierre et Marie Curie, Cure Parkinson Foundation, Rosetrees Trust, Parkinson UK, and National Parkinson Foundation, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale.

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Serge Przedborski, Center for Motor Neuron Biology and Disease, P&S 5-420, Columbia University, 630 West 168th Street, New York, NY 10032; sp30@columbia.edu

Abstract

Parkinson's disease is a common adult-onset neurodegenerative disorder whose pathogenesis remains essentially unknown. Currently, it is believed that the neurodegenerative process in Parkinson's disease is a combination of both cell-autonomous and non-cell-autonomous mechanisms. Proposed cell-autonomous mechanisms include alterations in mitochondrial bioenergetics, dysregulation of calcium homeostasis, and impaired turnover of mitochondria. As for the proposed non-cell-autonomous mechanisms, they involve prion-like behavior of misfolded proteins and neuroinflammation. This suggests that cell death in Parkinson's disease is caused by a multifactorial cascade of pathogenic events and argues that effective neuroprotective therapy for Parkinson's disease may have to rely on multiple drug interventions. © 2013 Movement Disorder Society

Ancillary