biostudies-literatureMontresor SDeutsche Forschungsgemeinschafte16214https://www.ebi.ac.uk/biostudies/studies/S-EPMC11657929biostudies-literatureUnknown169(1)Chaperones safeguard protein homeostasis by promoting folding and preventing aggregation. HSP110 is a cytosolic chaperone that functions as a nucleotide exchange factor for the HSP70 cycle. Together with HSP70 and a J-domain protein (JDP), HSP110 maintains protein folding and resolubilizes aggregates. Interestingly, HSP110 is vital for the HSP70/110/JDP-mediated disaggregation of amyloidogenic proteins implicated in neurodegenerative diseases (i.e., α-synuclein, HTT, and tau). However, despite its abundance, HSP110 remains still an enigmatic chaperone, and its functional spectrum is not very well understood. Of note, the disaggregation activity of neurodegenerative disease-associated amyloid fibrils showed both beneficial and detrimental outcomes in vivo. To gain a more comprehensive underJournal of neurochemistryHSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity.PMC11657929KI1988/3-2KI1988/7‐1KI1988/7-1KI1988/3‐2Kelkar ABasilicata LKirstein JKulkarni NSecker LPigazzini MLBaskaran SMontresor SSleiman MAdhikari GJacob NSpellerberg PKalsi GKEhlert YfalseHSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity.Chaperones safeguard protein homeostasis by promoting folding and preventing aggregation. HSP110 is a cytosolic chaperone that functions as a nucleotide exchange factor for the HSP70 cycle. Together with HSP70 and a J-domain protein (JDP), HSP110 maintains protein folding and resolubilizes aggregates. Interestingly, HSP110 is vital for the HSP70/110/JDP-mediated disaggregation of amyloidogenic proteins implicated in neurodegenerative diseases (i.e., α-synuclein, HTT, and tau). However, despite its abundance, HSP110 remains still an enigmatic chaperone, and its functional spectrum is not very well understood. Of note, the disaggregation activity of neurodegenerative disease-associated amyloid fibrils showed both beneficial and detrimental outcomes in vivo. To gain a more comprehensive under2025-01-01T00:00:00Z2025 Jan2025-04-04T21:45:39.285Z2025-04-04T21:45:39.285ZS-EPMC116579293918025510.1111/jnc.16214