HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsRudolf A Kley, Peter F M van der Ven, Montse Olivé, Jörg Höhfeld, Lev G Goldfarb, Dieter O Fürst, Matthias Vorgerd
JournalAutophagy (Autophagy) Vol. 9 Issue 3 Pg. 422-3 (Mar 2013) ISSN: 1554-8635 [Electronic] United States
PMID23238331 (Publication Type: Journal Article)
Chemical References
  • Contractile Proteins
  • FLNC protein, human
  • Filamins
  • Heat-Shock Proteins
  • Microfilament Proteins
  • Molecular Chaperones
  • Ubiquitin
  • Proteasome Endopeptidase Complex
Topics
  • Cells, Cultured
  • Contractile Proteins (genetics)
  • Filamins
  • Heat-Shock Proteins (metabolism)
  • Humans
  • Microfilament Proteins (genetics)
  • Molecular Chaperones (metabolism)
  • Muscle, Skeletal (pathology)
  • Muscular Diseases (genetics, metabolism)
  • Mutation
  • Myofibrils (pathology)
  • Proteasome Endopeptidase Complex (metabolism)
  • Proteolysis
  • Ubiquitin (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: