Novel small molecule derivatives improve survivability in the cellular model of Huntington's disease <i>via</i> improving mitochondrial fusion.

ABSTRACT: Mitochondrial dysfunction is one of the primary cellular conditions involved in developing Huntington's disease (HD) pathophysiology. The accumulation of mutant huntingtin protein with abnormal PolyQ repeats resulted in the death of striatal neurons with enhanced mitochondrial fragmentation. In search of neuroprotective molecules against HD conditions, we synthesized a set of isoxazole-based small molecules to screen their suitability as beneficial chemicals improving mitochondrial health. Systematic characterization of one of these isoxazole derivatives, C-5, demonstrated improved mitochondrial health with reduced apoptosis via rebalancing fission-fusion dynamics in HD condition. Gene and protein expression analysis confirmed that C-5 treatment enhanced the expression of mitochondr

SUBMITTER: Kodam P 

PROVIDER: S-EPMC12415771 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature