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- Title
Rapamycin-induced autophagy aggravates pathology and weakness in a mouse model of VCP-associated myopathy.
- Authors
Ching, James K; Weihl, Conrad C
- 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.
- Publication
Autophagy, 2013, Vol 9, Issue 5, p799
- ISSN
1554-8635
- Publication type
Journal Article
- DOI
10.4161/auto.23958