Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: implications for human motor neuron disease.

ABSTRACT:

Background

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS.

Results

In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enl

SUBMITTER: Palmisano R 

PROVIDER: S-EPMC3058068 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature