Guan Lab

Department of Computational Medicine & Bioinformatics
Fri, 09/30/2016 - 09:19 -- gyuanfan
TitleRescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing.
Publication TypeJournal Article
Year of Publication2016
AuthorsGiorgetti E, Yu Z, Chua JP, Shimamura R, Zhao L, Zhu F, Venneti S, Pennuto M, Guan Y, Hung G, Lieberman AP
JournalCell Rep
Volume17
Issue1
Pagination125-36
Date Published2016 Sep 27
ISSN2211-1247
Abstract

Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

DOI10.1016/j.celrep.2016.08.084
Comment

http://www.ncbi.nlm.nih.gov/pubmed/27681426?dopt=Abstract

Alternate JournalCell Rep
PubMed ID27681426