Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

Int J Mol Sci. 2020 Feb 19;21(4):1409. doi: 10.3390/ijms21041409.

Abstract

Skeletal muscle and the nervous system depend on efficient protein quality control, and they express chaperones and cochaperones at high levels to maintain protein homeostasis. Mutations in many of these proteins cause neuromuscular diseases, myopathies, and hereditary motor and sensorimotor neuropathies. In this review, we cover mutations in DNAJB6, DNAJB2, αB-crystallin (CRYAB, HSPB5), HSPB1, HSPB3, HSPB8, and BAG3, and discuss the molecular mechanisms by which they cause neuromuscular disease. In addition, previously unpublished results are presented, showing downstream effects of BAG3 p.P209L on DNAJB6 turnover and localization.

Keywords: J-domain protein; heat shock protein; myopathy; neuropathy; pathomechanism.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Gene Expression Regulation / genetics
  • HSP40 Heat-Shock Proteins / chemistry
  • HSP40 Heat-Shock Proteins / genetics
  • HSP40 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism*
  • Muscular Diseases / pathology
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / metabolism*
  • Neuromuscular Diseases / pathology
  • Signal Transduction / genetics
  • alpha-Crystallin B Chain / genetics
  • alpha-Crystallin B Chain / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • CRYAB protein, human
  • DNAJB2 protein, human
  • DNAJB6 protein, human
  • HSP40 Heat-Shock Proteins
  • HSPB1 protein, human
  • HSPB3 protein, human
  • HSPB9 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • alpha-Crystallin B Chain