Convergent pathobiologic model of Parkinson's disease.
The etiology of Parkinson's disease (PD) has yet to be delineated. Human genetic studies as well as neurotoxicant and transgenic animal models of PD suggest that multiple events trigger the initiation of this progressive age-related neurodegenerative disorder. In addition, we propose that despite disparate disease triggers a convergent pathobiologic pathway exists leading to cell death. The common pathway model posits that both familial and sporadic forms of Parkinson's disease obligately share a common pathophysiological substrate. Herein we discuss the evidence for a common pathway model of Parkinson's disease through a review of synuclein transgenic models and outline an approach for the identification of shared therapeutic targets. We end with a discussion of a potential alternative therapy for Parkinson's disease.
Maguire-Zeiss
Kathleen A
KA
Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Federoff
Howard J
HJ
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D051843:Synucleins
D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D051843:Synucleins