A Chaperome Subnetwork Safeguards Proteostasis in Aging and Neurodegenerative Disease

Chaperones are central to the proteostasis network (PN) and safeguard the proteome from misfolding, aggregation, and proteotoxicity. We categorized the human chaperome of 332 genes into network communities using function, localization, interactome, and expression data sets. During human brain aging, expression of 32% of the chaperome, corresponding to ATP-dependent chaperone machines, is repressed, whereas 19.5%, corresponding to ATP-independent chaperones and co-chaperones, are induced. These repression and induction clusters are enhanced in the brains of those with Alzheimer's, Huntington's, or Parkinson's disease. Functional properties of the chaperome were assessed by perturbation in C. elegans and human…

• NI
  National Institutes of Health
• NI
  National Institute of Mental Health
• NH
  National Human Genome Research Institute