Berbamine hydrochloride as a brain penetrant galectin 3 inhibitor in a model of Huntington's disease - PubMed
4 hours ago
- #galectin-3 inhibitor
- #Huntington's disease
- #neurodegeneration
- Berbamine hydrochloride identified as a brain penetrant galectin-3 (Gal3) inhibitor.
- Gal3 is a key driver of microglial activation and neuroinflammation in neurodegenerative disorders.
- High-content imaging platform developed to screen compounds affecting Gal3 puncta formation.
- Berbamine hydrochloride disrupts Gal3 oligomerization and Gal3-TREM2 interaction via an allosteric mechanism.
- The compound showed therapeutic benefits in the R6/2 mouse model of Huntington's disease (HD).
- Improvements included enhanced motor functions, reduced mutant huntingtin protein aggregation, and restored signaling pathways.
- Transcriptomic profiling identified Gal3 as a central regulatory hub in HD-associated networks.
- The study presents a novel screening strategy for discovering intracellular Gal3 modulators.