Journal
AUTOPHAGY
Volume 9, Issue 5, Pages 799-800Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.23958
Keywords
rapamycin; MTOR; autophagy; VCP; myopathy
Categories
Funding
- NIA NIH HHS [R01 AG031867, K02 AG042095] Funding Source: Medline
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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.
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