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Autophagy. 2013 Mar;9(3):422-3. doi: 10.4161/auto.22921. Epub 2012 Dec 13.

Impairment of protein degradation in myofibrillar myopathy caused by FLNC/filamin C mutations.

Author information

  • 1Department of Neurology, Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany. rudolf.kley@rub.de

Abstract

Myofibrillar myopathy caused by FLNC/filamin C mutations is characterized by disintegration of myofibrils and a massive formation of protein aggregates within skeletal muscle fibers. We performed immunofluorescence studies in skeletal muscle sections from filaminopathy patients to detect disturbances of protein quality control mechanisms. Our analyses revealed altered expression of chaperone proteins and components of proteasomal and autophagic degradation pathways in abnormal muscle fibers that harbor protein deposits but not in neighboring muscle fibers without pathological protein aggregation. These findings suggest a dysfunction of protein stabilizing and degrading mechanisms that leads to a pathological accumulation of protein aggregates in abnormal fibers. Accordingly, a pharmacological modulation of chaperone activity may be a promising therapeutic strategy to prevent protein aggregation and to reduce disease progression. Newly established filaminopathy cell culture models provide a suitable basis for testing such pharmacological approaches.

KEYWORDS:

autophagy; chaperone-associated selective autophagy; filaminopathy; heat shock proteins; immunolocalization studies; myofibrillar myopathy; ubiquitin proteasome system

PMID:
23238331
PMCID:
PMC3590265
DOI:
10.4161/auto.22921
[PubMed - indexed for MEDLINE]
Free PMC Article
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