Therapeutic Potential of MCC950 in Restoring Autophagy and Cognitive Function in STZ-Induced Rat Model of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide. In this study, we explored the critical role of autophagy in AD pathology using a streptozotocin (STZ)-induced AD model in Wistar rats. The experimental groups included sham, STZ-induced AD, and STZ + MCC950-treated animals. Our findings revealed that administering two doses of STZ (3 mg/kg) intracerebroventricular at the interval of 48 h (on days 0 and 2), triggered autophagy, as evidenced by elevated levels of autophagy markers such as LC3II, ULK1, Beclin1, Ambra1, Cathepsin B, and a reduction in p62 levels. Behavioral assessments, including the water maze and novel object recognition tests, confirmed cognitive deficits and memory impairment, while the open-field test indicated increased anxiety in STZ-induced AD rats. In particular, treating the STZ-induced AD group with MCC950 (50 mg/kg) decreased the overexpression of autophagy-related proteins, which was consistent with better behavioral outcomes and lower anxiety. Overall, this study highlights new insights into AD pathophysiology and suggests potential therapeutic avenues.