NEW 2. The cytoprotective protein MANF promotes neuronal

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NEW 2. The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor
J Biol Chem . 2021 Jan 15;100295. doi: 10.1016/j.jbc.2021.100295.

"Here we show for the first time that MANF promotes the survival of ER-stressed neurons in vitro as a general unfolded protein response (UPR) regulator, affecting several UPR pathways simultaneously. Interestingly, MANF does not affect naïve neurons. We hypothesize that MANF regulates UPR signaling towards a mode more compatible with neuronal survival....Interestingly, functional analysis of the antiapoptotic properties of MANF mutants in cultured neurons revealed divergent roles of MANF as a GRP78 cofactor and as an antiapoptotic regulator of UPR. We conclude that the co-factor type interaction with GRP78 is dispensable for the survival-promoting activity of MANF in neurons."

https://pubmed.ncbi.nlm.nih.gov/33460650/

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