FMP-6-S4 impeded Aβ42 induced SH-SY5Y cell injury by targeting cyclophilin D

Abstract

Amyloid β (Aβ) is pivotal in the progression of Alzheimer’s disease (AD) by inducing neuron damage. Recent evidences implied that the formation of mitochondrial permeability transition pore (mPTP) was involved in Aβ-mediated mitochondrial dysfunction. Cyclophilin D (CypD), which is the essential component of mPTP, could interact with Aβ and promote mPTP formation, resulting in severe mitochondrial dysfunction and eventually cell death. In this study, we demonstrated that a glycopeptide, FMP-6-S4, purified from the fruit of Fructus Mori bond to CypD and suppressed its expression. Furthermore, FMP-6-S4 markedly inhibited the opening of mPTP, the generation of reactive oxygen species and calcium releasing. Mechanistically study showed that FMP-6-S4 could bind to CypD to disrupt the interaction between CypD and Aβ42. Finally, FMP-6-S4 could bind to Aβ42 directly then attenuate cell damage induced by Aβ42 via p53-puma signaling pathway. Together, our results suggest FMP-6-S4 might be a potential candidate for anti-AD drug development.

Keywords

• Alzheimer’s disease
• Fructus Mori
• Amyloid β
• Cyclophilin D
• Mitochondrial permeability transition pore
• Glycopeptide