Neuroprotective and gut health benefits of Ugni molinae in preclinical Huntington's disease models.

Abstract

Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by an unstable trinucleotide CAG repeat expansion at the N-terminus of the IT-15 gene, which encodes the ∼350 kDa huntingtin protein (Htt). This mutation confers toxic properties, promoting neuronal dysfunction and death through multiple mechanisms. Effective treatments for HD are still lacking. Therefore, early-stage interventions could represent a promising approach to addressing the pathological aspects of HD. Recently, our laboratory explored the potential neuroprotective effect of murtilla (Ugni molinae, Turcz) fruit extract (ETE 19-1) in an HD cellular model and observed a significant anti-aggregation effect on mutant Htt (mHtt). In this study, we determine the beneficial effects of ETE 19-1 on HD progression in both brain and gut tissues. Our results show that a ETE 19-1 reduces motor impairment, decreases mHtt levels, and mitigates microglia activation in the striatum brain region of R6/2 mice. Moreover, we observed a reduction in gastrointestinal inflammation and an increase the gut microbiota biodiversity in R6/2 mice treated with ETE 19-1 extract. These findings highlight the impact of polyphenol-enriched natural products on the brain and gut inflammatory process during the progression of neurodegenerative diseases.