Gene dosage and pathogenesis of Parkinson's disease

JL Eriksen, S Przedborski, L Petrucelli - Trends in molecular medicine, 2005 - cell.com
JL Eriksen, S Przedborski, L Petrucelli
Trends in molecular medicine, 2005cell.com
Four recent papers related specifically to the familial form of Parkinson's disease reinforce
the idea that endogenous levels of α-synuclein can strongly influence disease phenotype.
Two recent publications of α-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 α-synuclein, potentially resulting in elevated levels of α-synuclein …
Four recent papers related specifically to the familial form of Parkinson's disease reinforce the idea that endogenous levels of α-synuclein can strongly influence disease phenotype. Two recent publications of α-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 α-synuclein, potentially resulting in elevated levels of α-synuclein. Conversely, the complete knockout of SNCA has little effect on transgenic mice. It is now clear that the regulation of α-synuclein levels has potential significance in the pathogenesis and treatment of sporadic PD.
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