The therapeutic potential of (R)-carvedilol in Huntington's disease through enhancement of autophagy-lysosomal pathway via GSK-3β inhibition.

ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the huntingtin (Htt) gene, leading to the aggregation of mutant huntingtin protein (mHTT) in cells, particularly in cortical and striatal neurons. This results in involuntary movements, cognitive impairment, and emotional instability. One of the critical pathogenic mechanisms in HD is impaired autophagy, which plays a vital role in cellular homeostasis by degrading damaged organelles and misfolded proteins through the formation of autophagosomes that fuse with lysosomes. However, the aggregation of mHTT disrupts autophagic function, leading to the accumulation of mHTT and exacerbating the disease's pathogenesis. Carvedilol is an established clinical medication used to treat hyperten

SUBMITTER: Cheng CY 

PROVIDER: S-EPMC12047517 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature