Chaperome

Chaperome refers to the ensemble of all cellular molecular chaperone and co-chaperone proteins that assist protein folding of misfolded proteins or folding intermediates in order to ensure native protein folding and function, to antagonize aggregation-related proteotoxicity and ensuing protein loss-of-function or protein misfolding-diseases such as the neurodegenerative diseases Alzheimer's, Huntington's or Parkinson's disease, as well as to safeguard cellular proteostasis and proteome balance.[1][2]

The term chaperome was first coined in a 2006 publication in Cell by Balch and co-workers on the finding that down-regulation of the Hsp90 co-chaperone Aha1 rescues misfolding of CFTR in cystic fibrosis to describe the overall chaperone folding environment, or the "chaperome".[3] In 2014, Brehme and co-workers systematically studied the expression dynamics of the full human chaperome comprising ~300 human chaperones and co-chaperones in human aging brains and in brains of patients with neurodegenerative diseases. Integration with chaperome-wide functional RNA interference (RNAi) perturbation experiments in worm and in human cells led to the identification of a chaperome sub-network that safeguards proteostasis in aging and neurodegenerative diseases.[4]

Recently, a comprehensive literature survey reviewed the literature since the release of the human genome sequence in 2000 for systematic studies in small animal model systems and highlighted the power of model systems to unveil those key chaperone modifiers of proteotoxicity out of the large number represented in the wider human chaperome that could inform targets and strategies for therapeutic regulation of chaperone functionality.[5]

See also

References

  1. ↑ Balch WE, Morimoto RI, Dillin A, Kelly JW (Feb 2008). "Adapting proteostasis for disease intervention". Science. 319 (5865): 916–919. Bibcode:2008Sci...319..916B. doi:10.1126/science.1141448. PMID 18276881.
  2. ↑ Douglas, P. M.; Summers, D. W.; Cyr, D. M. (2009). "Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways". Prion. 3 (2): 51–58. doi:10.4161/pri.3.2.8587. PMC 2712599Freely accessible. PMID 19421006.
  3. ↑ Wang X, et al. (2006). "Hsp90 cochaperone Aha1 down regulation rescues misfolding of CFTR in cystic fibrosis". Cell. 127 (4): 803–15. doi:10.1016/j.cell.2006.09.043. PMID 17110338.
  4. ↑ Brehme M, et al. (2014). "A conserved chaperome sub-network safeguards protein homeostasis in aging and neurodegenerative disease". Cell Rep. 9 (3): 1135–1150. doi:10.1016/j.celrep.2014.09.042. PMC 4255334Freely accessible. PMID 25437566.
  5. ↑ Brehme M, Voisine C (2016). "Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity". Dis Model Mech. 9 (8): 823–38. doi:10.1242/dmm.024703. PMC 5007983Freely accessible. PMID 27491084.
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