Pathogenesis of Parkinson's disease
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; firstname.lastname@example.org
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