Send to

Choose Destination
Oncotarget. 2016 Mar 22;7(12):13354-71. doi: 10.18632/oncotarget.7997.

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

Author information

Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Institut de Neuropatologia, Servei Anatomia Patològica, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
Department of Neurology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.


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 that may underlie toxicity. We observed that p-Akt levels are reduced in step with an increase in apoptotic markers in GNE myopathy myoblasts compared to control myoblasts. The same results were experimentally obtained when Aβ1-42 was overexpressed in myotubes. Hence, we propose a novel disease mechanism whereby hyposialylation favors Aβ1-42 internalization and the subsequent apoptosis in myotubes and in skeletal muscle from GNE myopathy patients.


Akt; Aβ; GNE myopathy; Gerotarget; apoptosis; endocytosis

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center