Lycium barbarum glycopeptide alleviates the neuropathology in Huntington’s disease mouse models

Abstract Huntington’s disease is a hereditary neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the huntingtin ( HTT ) gene. The clinical manifestations of Huntington’s disease include motor dysfunction, as well as psychiatric and cognitive impairments. The misfolding and aggregation of the mutated HTT protein in the central nervous system led to neuronal damage and death. Currently, there is a lack of effective clinical treatments to slow the progression of Huntington’s disease. Lycium barbarum (goji berry) is a traditional Chinese herbal medicine, and its purified active component, Lycium barbarum glycopeptide, has been shown to alleviate neuropathology in various neurodegenerative diseases. Here, we evaluated the therapeutic potential of Lycium barbarum glycopeptide in Huntington’s disease using both in vitro and in vivo models. We found that Lycium barbarum glycopeptide treatment effectively reduced mutated HTT aggregation in cellular models, and in Huntington’s disease mice, it significantly improved motor dysfunction, reduced mutated HTT aggregation, ameliorated autophagic dysfunction, and attenuated gliosis. These results suggest that Lycium barbarum glycopeptide reduces mutated HTT aggregation through the restoration of autophagy function, positioning it as a promising candidate for Huntington’s disease therapy with potential for clinical translation.