Vilazodone ameliorates senescence-related Alzheimer's disease like symptoms by targeting Plau to induce autophagy in senescent cells.

Abstract

Alzheimer's disease (AD), a neurodegenerative disease, has been linked to cellular senescence. Elimination of senescent cells through pharmacological and genetic could enhance memory performance of patient with AD. Despite extensive research, its complexity remains a significant challenge, leaving us without an effective remedy so far. In this study, by utilizing adeno-associated virus, we successfully suppressed the expression of Plau in mice with AD, providing further evidence for its significant contribution to the initiation and progression of this neurodegenerative disorder. Mechanistically, the activation of Cox-2 expression by Plau leads to the induction of senescence in neuronal cells. By specifically targeting the Plau in senescent cells, vilazodone, a novel inhibitor of Plau, can effectively trigger autophagy in these senescence cells and thereby eliminate them from the system. Additional in vivo studies demonstrated the potential of vilazodone to enhance cognitive function and memory in mice with AD, suggesting its therapeutic efficacy for treating AD. The results indicate that focusing on Plau may offer a hopeful approach for treating AD. Additionally, exploring the ability to inhibit Plau and alter the structure of vilazodone could provide valuable knowledge for developing drugs aimed at targeting Plau in AD-related conditions.