Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential - PubMed
6 hours ago
- #heat shock proteins
- #proteostasis
- #neurodegeneration
- Heat shock proteins Hsp70 and Hsp90 play crucial roles in maintaining protein homeostasis (proteostasis) in neurons.
- Declining proteostasis with age contributes to neurodegenerative diseases like Alzheimer's, Parkinson's, ALS, and Huntington's disease.
- Hsp70 and Hsp90 regulate protein folding, refolding, and degradation, and their dysfunction is linked to pathogenic protein aggregation.
- The review discusses the structural features, isoforms, and interactions of Hsp70 and Hsp90, including their ATP-driven chaperone cycles and co-chaperone networks.
- Age-related declines in chaperone expression and HSF-1 activity lead to proteostasis collapse and increased neuronal vulnerability.
- Therapeutic strategies targeting Hsp70 and Hsp90 include small-molecule modulators, co-chaperone inhibitors, and recombinant chaperone therapy.
- These therapies aim to restore proteostasis and cognitive function, highlighting the dual role of Hsp70/Hsp90 in neurodegeneration.