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 journalArticlepeer-review

30 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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