Rapamycin-induced autophagy aggravates pathology and weakness in a mouse model of VCP-associated myopathy

James K. Ching, Conrad C. Weihl

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Pathological phenotypes in inclusion body myopathy (IBM) associated with Paget disease of the bone (PDB), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (IBMPFD/ALS) include defective autophagosome and endosome maturation that result in vacuolation, weakness and muscle atrophy. The link between autophagy and IBMPFD/ALS pathobiology has been poorly understood. We examined the AKT-FOXO3 and MTOR pathways to characterize the regulation of autophagy in IBMPFD/ALS mouse muscle. We identified a defect in MTOR signaling that results in enhanced autophagosome biogenesis. Modulating MTOR signaling may therefore be a viable therapeutic target in IBMPFD/ALS.

Original languageEnglish
Pages (from-to)799-800
Number of pages2
JournalAutophagy
Volume9
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Autophagy
  • MTOR
  • Myopathy
  • Rapamycin
  • VCP

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