Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances.

ABSTRACT: Intracellular accumulations of altered, misfolded proteins in neuronal and other cells are pathological hallmarks shared by many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in several genes give rise to familial forms of ALS. Mutations in Sigma receptor 1 have been found to cause a juvenile form of ALS and frontotemporal lobar degeneration (FTLD). We recently described altered localization, abnormal modification and loss of function of SigR1 in sporadic ALS. In order to further elucidate the molecular mechanisms underlying SigR1-mediated alterations in sporadic and familial ALS, we extended our previous studies using neuronal SigR1 knockdown cell lines. We found that loss of SigR1 leads to abnormal ER morphology, mitochondrial abnormalities and impai

SUBMITTER: Vollrath JT 

PROVIDER: S-EPMC4611717 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature