Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3 β pathway.

In this study, we showed that MANF up-regulates the expression of nuclear factor erythroid 2-related factor (Nrf2) and promotes its translocation into the nucleus. The anti-oxidation and anti-apoptotic effects of MANF could be partially blocked by inhibitor or shRNA-mediated knockdown of Nrf2. Furthermore, MANF activated phospoinositide-3-kinase (PI3K)/Akt signaling and suppressed glycogen synthase kinase (GSK3β) activation. PI3K inhibitor (LY49002) abolished effects of MANF on AKT phosphorylation, GSK3β inactivation, Nrf2 nuclear translocation and subsequently abrogated MANF-mediates cytoprotection. Collectively, our findings indicated that MANF-mediated protection against 6-OHDA-induced cytotoxicity by potentiating the Nrf2-related survival mechanism through the PI3K/Akt/GSK3β pathway. PMID: 29079145 [PubMed - as supplied by publisher]

https://www.ncbi.nlm.nih.gov/pubmed/29079145?dopt=Abstract

Source: Experimental Gerontology - October 24, 2017 Category: Geriatrics Authors: Zhang J, Tong W, Sun H, Jiang M, Shen Y, Liu Y, Gu H, Guo J, Fang J, Jin L Tags: Exp Gerontol Source Type: research