title: Gene dosage and pathogenesis of Parkinson's disease.
abstract: Four recent papers related specifically to the familial form of Parkinson's disease reinforce the idea that endogenous levels of alpha-synuclein can strongly influence disease phenotype. Two recent publications of alpha-synuclein-duplication mutations show that the severity of familial Parkinsonian phenotype is dependent upon SNCA gene dosage and corresponding protein levels. Familial point mutations in SNCA were found to impair the efficient lysosomal degradation of alpha-synuclein, potentially resulting in elevated levels of alpha-synuclein. Conversely, the complete knockout of SNCA has little effect on transgenic mice. It is now clear that the regulation of alpha-synuclein levels has potential significance in the pathogenesis and treatment of sporadic PD.
authors.affiliation: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Eriksen
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
authors.forename: Leonard
authors.initials: L
authors.lastname: Petrucelli
mesh_terms: D000818:Animals; D018628:Gene Dosage; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D017354:Point Mutation / Q000235:genetics; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein