Clearance of variant Creutzfeldt-Jakob disease prions in vivo by the Hsp70 disaggregase system.

ABSTRACT: The metazoan Hsp70 disaggregase protects neurons from proteotoxicity that arises from the accumulation of misfolded protein aggregates. Hsp70 and its co-chaperones disassemble and extract polypeptides from protein aggregates for refolding or degradation. The effectiveness of the chaperone system decreases with age and leads to accumulation rather than removal of neurotoxic protein aggregates. Therapeutic enhancement of the Hsp70 protein disassembly machinery is proposed to counter late-onset protein misfolding neurodegenerative disease that may arise. In the context of prion disease, it is not known whether stimulation of protein aggregate disassembly paradoxically leads to enhanced formation of seeding competent species of disease-specific proteins and acceleration of neurodegenerative di

SUBMITTER: Thackray AM 

PROVIDER: S-EPMC9473358 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature