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Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a …