The roles of HSP40/DNAJ protein family in neurodegenerative diseases

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Nov 25;51(5):640-646. doi: 10.3724/zdxbyxb-2021-0406.


Molecular chaperones and co-chaperones facilitate the assembly of newly synthesized polypeptides and refolding of unfolded or misfolded proteins, thereby maintaining protein homeostasis in cells. As co-chaperones of the master chaperone heat shock protein (HSP) 70, the HSP40 (DNAJ) proteins are largest chaperone family in eukaryotic cells. They contain a characteristic J-domain which mediates interaction with HSP70, thereby helping protein folding. It is well perceived that protein homeostasis is vital for neuronal health. DNAJ family proteins have been linked to the occurrence and progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinocerebellar ataxia, Charcot-Marie-Tooth disease, spinal muscular atrophy, distal hereditary motor neuropathy, limb-girdle type muscular dystrophy, neuronal ceroid lipofuscinosis and essential tremor in recent studies. DNAJA1 effectively degrades huntington aggregates; DNAJB1 can degrade protein aggregates ataxin-3; DNAJB2 can inhibit the formation of huntington aggregates; DNAJB6 can inhibit the aggregation of Aβ 42 and α-synuclein; DNAJC5 can promote the release of TDP-43, τ protein, and α-synuclein into the extracellular space. Mutations in the essential tremor-associated DNAJC13 gene can prevent endosome protein trafficking. This article reviews the mechanism of DNAJ protein family in neurodegenerative diseases.

Keywords: DNAJ; HSP40; Molecular chaperones; Neurodegenerative diseases; Protein homeostasis; Review.

Publication types

  • Review

MeSH terms

  • Essential Tremor*
  • HSP40 Heat-Shock Proteins / genetics
  • Humans
  • Molecular Chaperones / metabolism
  • Nerve Tissue Proteins
  • Neurodegenerative Diseases*
  • Protein Folding
  • alpha-Synuclein / metabolism


  • HSP40 Heat-Shock Proteins
  • alpha-Synuclein
  • DNAJB1 protein, human
  • DNAJB6 protein, human
  • Nerve Tissue Proteins
  • Molecular Chaperones
  • DNAJB2 protein, human

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