Molecular chaperones mediated proteostasis depletion: A cause of neurodegeneration?
A focused review examining how chaperones (Hsp90, Hsp110, Hsp27, and DJ-1) regulate proteostasis and how their dysfunction may contribute to neurodegenerative diseases including Parkinson's, with discussion of mechanisms for folding, aggregation prevention, and degradation pathways.
What the AI sees
A focused review examining how chaperones (Hsp90, Hsp110, Hsp27, and DJ-1) regulate proteostasis and how their dysfunction may contribute to neurodegenerative diseases including Parkinson's, with discussion of mechanisms for folding, aggregation prevention, and degradation pathways.
Research significance
Highlights chaperone-based mechanisms (including the PD-linked DJ-1 and mitoprotection) that suggest actionable targets for modulating proteostasis, but remains a conceptual review with limited new experimental or translational data.
Source abstract
Protein homeostasis is a critical aspect of cellular homeostasis as proteins are one of the most diverse biomolecules, responsible for multiple molecular and cellular functions. Protein quality control machinery is essential for maintaining integrity of cellular proteome via regulating its synthesis, structure, function, and degradation. Molecular chaperones are central to the protein quality control apparatus of cells and assist in folding nascent polypeptides, maturation, sequestration, solubilisation, and degradation of proteins. The coordination and cooperation between multiple cellular chaperones and other quality control elements, such as ubiquitin-proteasome system and autophagy, form a network, critical for proteostasis. Disturbed proteostasis and protein aggregation are hallmark features of neurodegenerative diseases. Re-establishing cellular proteostasis and enhancing chaperones' levels and functions can alleviate protein aggregation and associated cytotoxicity. Here, we have explored the potential of abundant cellular chaperone Hsp90, large chaperone Hsp110, small chaperone Hsp27, and anti-oxidant and mitoprotective chaperone DJ-1 in the regulation of proteostasis, with implications for neurodegenerative diseases, Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. We have focused on roles and mechanisms of function of these chaperones in countering disturbed proteostasis in neurodegenerative disorders.