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Unfolded protein response and aggresome formation in hereditary reducing-body myopathy

Teerin Liewluck1, Yukiko K Hayashi, Maki Ohsawa

  • 1Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.

Muscle & Nerve
|November 14, 2006
PubMed

Insights

Reducing-body myopathy (RBM) is a rare genetic disorder. This study reveals that RBM involves protein misfolding within the endoplasmic reticulum, leading to the formation of unique reducing bodies.

Area of Science:

  • Muscle physiology and genetics
  • Cellular biology
  • Molecular medicine

Background:

  • Reducing-body myopathy (RBM) is a rare inherited muscle disease.
  • It is characterized by abnormal protein aggregates called reducing bodies (RBs) within muscle cells.

Observation:

  • RBs in RBM patients contain gamma-tubulin, ubiquitin, and endoplasmic reticulum (ER) chaperones.
  • Specific membrane proteins were also identified within these inclusions.
  • Elevated levels of glucose-related protein 78 (a molecular chaperone) were noted.

Findings:

  • The study characterized the aggresomal features of reducing bodies in a family with hereditary RBM.
  • Increased messenger ribonucleic acid and protein levels of glucose-related protein 78 were observed.
  • These findings link ER stress to RB formation.

Implications:

  • The unfolded protein response, triggered by misfolded protein accumulation in the ER, is implicated in RB formation.
  • Understanding this mechanism could lead to new therapeutic strategies for RBM.
  • This research sheds light on the cellular basis of rare myopathies.

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