Recent advances in the genetics and pathogenesis of Parkinson disease

摘要: The identification of three genes and several additional loci associated with inherited forms levodopa-responsive PD has confirmed that this is not a single disorder. Yet, analyses the structure function these gene products point to critical role protein aggregation in dopaminergic neurons substantia nigra as common mechanism leading neurodegeneration all known disease. specific identified date--alpha-synuclein, Parkin, ubiquitin C terminal hydrolase L1--are either closely involved proper functioning ubiquitin-proteasome pathway or are degraded by protein-clearing machinery cells. Knowledge gained from genetically transmitted also clear implications for nonfamilial Lewy bodies, even sporadic PD, contain products, particularly abundant amounts fibrillar alpha-synuclein. Increased alpha-synuclein oxidative stress, well oxidant-induced proteasomal dysfunction, link genetic potential environmental factors onset progression biochemical molecular cascades elucidated studies can provide novel targets curative therapies.