A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease (Adv. Sci. 8/2025)

Repurposing an Old Drug for Alzheimer's Disease In article number 2407812, Dong-Gyu Jo and co-workers propose a novel strategy for Alzheimer's disease (AD) treatment, demonstrating that the anticancer agent 6-thioguanosine (6-TG) interacts with the receptor for advanced glycation endproducts (RAGE) to regulate BACE1 expression, thereby reducing Aβ accumulation. The interaction with RAGE increases soluble RAGE (sRAGE) levels, which blocks Aβ-RAGE interactions and reduces neuroinflammatory responses. Increasing sRAGE levels could effectively inhibit the RAGE pathway and reduce Aβ accumulation.