ArticleBrain : a journal of neurology2026
Berbamine hydrochloride as a brain-penetrant galectin-3 inhibitor in a model of Huntington's disease.
Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Developing Galectin-3-Targeted Therapeutics in Diseases: Three Distinct Galectin-3 Segments for Targeting.Expert reviews in molecular medicine · 2026Review
- Neurotrophins and Galectin-3: Hidden Keys in Neuroinflammation-A Narrative Review.International journal of molecular sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Galectin-3 (Gal3) acts as an intracellular sensor of lysosomal damage and a key driver of microglial activation and neuroinflammation in multiple neurodegenerative disorders. Despite its biological importance, no inhibitors have been identified that both modulate intracellular Gal3 activity and effectively cross the blood-brain barrier. Here, we established an innovative high-content imaging platform using microglia expressing Gal3-GFP, allowing direct visualization of Gal3 puncta formation upon lysosomal damage as a phenotypic readout for compound screening. Through screening of ∼24 000 small molecules, we identified berbamine hydrochloride as a potent inhibitor of Gal3 puncta formation with confirmed blood-brain barrier permeability. Mechanistically, berbamine hydrochloride disrupts Gal3 oligomerization and Gal3-TREM2 interaction via a unique allosteric mechanism distinct from the canonical glycan-binding domain. It attenuated lipopolysaccharide-induced inflammation in vitro and achieved sustained brain exposure in vivo. In the R6/2 mouse model of Huntington's disease, berbamine hydrochloride effectively improved motor functions, reduced mutant huntingtin protein aggregation and restored crucial dopaminergic and ciliary signalling pathways. Transcriptomic profiling further identified Gal3 as a central regulatory hub within Huntington's disease-associated networks that were corrected upon treatment. Computational docking and molecular dynamics simulations further supported an allosteric binding mode distinct from the canonical glycan-binding domain of Gal3. Together, these findings establish berbamine hydrochloride as the first blood-brain barrier-penetrant small molecule inhibitor targeting intracellular Gal3 with therapeutic benefit in Huntington's disease. Furthermore, the puncta-based screening strategy that we developed provides a robust platform for discovering intracellular modulators of Gal3 relevant to a wide range of neurological diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.