Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration.

ABSTRACT: Mutations in components of the molecular motor dynein/dynactin lead to neurodegenerative diseases of the motor system or atypical parkinsonism. These mutations are associated with prominent accumulation of vesicles involved in autophagy and lysosomal pathways, and with protein inclusions. Whether alleviating these defects would affect motor symptoms remain unknown. Here, we show that a mouse model expressing low levels of disease linked-G59S mutant dynactin p150(Glued) develops motor dysfunction >8 months before loss of motor neurons or dopaminergic degeneration is observed. Abnormal accumulation of autophagosomes and protein inclusions were efficiently corrected by lowering dietary protein content, and this was associated with transcriptional upregulations of key players in autophagy. Mos

SUBMITTER: Wiesner D 

PROVIDER: S-EPMC4447824 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature