Increased amyloid β-peptide uptake in skeletal muscle is induced by hyposialylation and may account for apoptosis in GNE myopathy.

ABSTRACT: GNE myopathy is an autosomal recessive muscular disorder of young adults characterized by progressive skeletal muscle weakness and wasting. It is caused by a mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which encodes a key enzyme in sialic acid biosynthesis. The mutated hypofunctional GNE is associated with intracellular accumulation of amyloid β-peptide (Aβ) in patient muscles through as yet unknown mechanisms. We found here for the first time that an experimental reduction in sialic acid favors Aβ1-42 endocytosis in C2C12 myotubes, which is dependent on clathrin and heparan sulfate proteoglycan. Accordingly, Aβ1-42 internalization in myoblasts from a GNE myopathy patient was enhanced. Next, we investigated signal changes triggered by Aβ1-42 t

SUBMITTER: Bosch-Morato M 

PROVIDER: S-EPMC4924647 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature