Mitochondrial morphogenesis, distribution, and Parkinson disease: insights from PINK1.
The etiology of Parkinson disease (PD) has been assumed to be a complex combination of environmental factors, intrinsic cellular metabolic properties, and susceptible genetic alleles. The primary obstacles to the development of a neuroprotective therapy in PD include uncertainties with regard to the precise cause(s) of neuronal dysfunction and what to target. The discoveries of Mendelian genes associated with inherited forms of PD in the last 10 years have revolutionized the understanding of the cellular pathways leading to neuronal dysfunction. Common themes of the pathogenesis of PD are beginning to emerge with mitochondrial dysfunction at the center stage. In this review, we summarize our knowledge of the pathogenesis of PD, revisit some aspects of mitochondrial biology, and discuss the insights from the study of Pink1, a familial PD-associated gene. We propose that mitochondrial morphogenesis and distribution might be a novel and potential common paradigm for PD and other neurodegenerative disease research and that modulation of such mitochondrial processes may prove to be a valuable therapeutic avenue for PD.
Yang
Yufeng
Y
Department of Pathology, Stanford University School of Medicine, Stanford; Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
Lu
Bingwei
B
D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D011494:Protein Kinases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase
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