Luteolin as potential treatment for Huntington's disease: Insights from a transgenic mouse model

Abstract

Aims: The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. Methods: HD N171- 82Q transgenic and WT mice received luteolin or vehicle for treat ment at 6 weeks of age. The mice's body weight changes and survival rates were moni tored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. Results: Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle- treated HD group. Furthermore, the luteolin- treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin- treated HD mice compared to the vehicle- treated HD group. Conclusion: Luteolin holds promise as a therapeutic agent for improving survival out comes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interven tions that reverse HD pathology or slow down its progression.