Neurodegeneration in Parkinson's disease: genetics enlightens physiopathology.
Parkinson's disease (PD) is a severe neurodegenerative disorder of complex etiology and enigmatic physiopathology. In the past decade, the identification of genes involved in rare familial Parkinsonian syndromes has brought hope that understanding the functions of their products will provide insight into the molecular mechanisms responsible for neurodegeneration. The knowledge accumulated thus far has delineated two putative, potentially interconnected, disease-causing pathways: alpha-synuclein accumulation may be central to Parkinsonism due to alpha-synuclein gene defects, but possibly also to sporadic PD and other genetic forms presenting with Lewy bodies; altered mitochondrial physiology may be pivotal to Parkinsonian syndromes caused by parkin, PINK1, and possibly DJ-1 gene mutations. Adding new pieces to this fragmentary picture to determine to what extent sporadic PD and Parkinsonism due to distinct genetic causes share common pathogenic mechanisms remains a major challenge toward the development of future therapeutic strategies for these disabling disorders.
Corti
Olga
O
Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, France. olga.corti@upmc.fr
Fournier
Margot
M
Brice
Alexis
A
D004298:Dopamine / Q000378:metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000150:complications* / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D004298:Dopamine; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein