Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression.

ABSTRACT: The common age-related neurodegeneration of Parkinson's disease can result from dominant causes like increased dosage of vesicle-associated alpha-synuclein (SNCA) or recessive causes like deficiency of mitophagy factor PINK1. Interactions between these triggers and their convergence onto shared pathways are crucial, but currently conflicting evidence exists. Here, we crossed previously characterized mice with A53T-SNCA overexpression and with Pink1 deletion to generate double mutants (DMs). We studied their lifespan and behavior, histological and molecular anomalies at late and early ages. DM animals showed potentiated phenotypes in comparison with both single mutants (SMs), with reduced survival and strongly reduced spontaneous movements from the age of 3 months onwards. In contrast to SM

SUBMITTER: Gispert S 

PROVIDER: S-EPMC4986551 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature