Geniposide protection against Aß1-42 toxicity correlates with mTOR inhibition and enhancement of autophagy.

Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer's disease. The present paper's goal was to explore the potential mechanisms of geniposide to protect against Alzheimer's disease. We treated the human neuroblastoma SH-SY5Y cell line with Aß1-42 as an Alzheimer's disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer's disease. Further, SH-SY5Y cells damaged by Aß1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aß1-42-induced toxicity. Results showed that Akt and mTOR's geniposide inhibited phosphorylation induced by Aß1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aß1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aß toxicity.

[Roles of Mammalian Target of Rapamycin Signaling and Autophagy Pathway in Alzheimer's Disease].

The mammalian target of rapamycin(mTOR)is a serine/threonine protein kinase that regulates protein synthesis and degradation,cytoskeletal formation,and cell longevity.Autophagy,a catabolic process necessary for the maintenance of intracellular homeostasis,is essential for cell survival,whereas mTOR is the crucial regulator of autophagy.Alzheimer's disease(AD)is the most common cause of progressive dementia in the elderly.It has been shown that disorders of mTOR and autophagy signaling pathways are closely related to AD.In the present review,we describe the regulatory roles of mTOR signaling and autophagy pathway in AD brain and introduce drugs for AD acting via modulation of autophagy and mTOR.

Semaglutide-mediated protection against Aß correlated with enhancement of autophagy and inhibition of apotosis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue with an extended half-life of approximately 1 week has being come into clinic trial to treat parkingson's disease but little is known about its effect to prevent against Alzheimer's disease (AD). The goal of the present study was to explore the potential mechanisms of semaglutide to protect against AD. METHODS: We treated SH-SY5Y cell line with Aß25-35 as an AD model. Further, SH-SY5Y cells damaged by Aß25-35 were treated by semaglutide. Autophagy-related proteins and apoptosis-related proteins were measured to explore molecular mechanisms for semaglutide to protect against Aß25-35. RESULTS: Semaglutide enhanced autophagy by increasing the expression of LC3II, Atg7, Beclin-1 and P62 which were inhibited by Aß25-35. Further we showed that semaglutide inhibited apoptosis by inhibiting the expression of Bax induced by Aß25-35 and increasing the expression of Bcl2 inhibited by Aß25-35. CONCLUSION: Our results provide a clue for the hypothesis that autophagy enhancement and apoptosis inhibition may be involved in the effect of semaglutide to protect against Aß 25-35.