HAP/ClpP-mediated disaggregation and degradation of Mutant SOD1 aggregates: A potential therapeutic strategy for Amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by the accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) protein aggregates in motor neurons, leading to progressive motor dysfunction and ultimately death. While the molecular chaperone heat shock protein 104 (Hsp104) has been shown to reduce protein misfolding by disaggregating protein aggregates, fully degrading these disaggregated proteins remains a significant challenge. In this study, we have investigated the effects of Hsp104 and its hyperactive variant, HAP, in combination with caseinolytic protease P (CIpP), on the disaggregation and degradation of SOD1 aggregates.