mesencephalic astrocyte-derived neurotrophic factor

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secreted, ER-resident neurotrophic protein with a bipartite structure consisting of an N-terminal saposin-like domain and a C-terminal SAP-like domain with an ER retention motif, mechanistically distinct from classical neurotrophins such as NGF and BDNF.[2][3] MANF modulates endoplasmic reticulum stress and the unfolded protein response, promotes neuronal survival, and exerts anti-apoptotic and anti-inflammatory effects, in part via PI3K/Akt/GSK3β–Nrf2 signaling and regulation of ER stress pathways.[2][3] In rodent models, recombinant MANF protein or gene-delivered MANF protects and restores dopaminergic neurons in Parkinson’s disease toxin models, reduces infarct size and improves functional recovery after cerebral ischemia, and shows benefit in models of traumatic CNS injury, Alzheimer’s disease, spinocerebellar ataxia, cardiac ischemia, and retinal degeneration, but as of now recombinant MANF has not entered human clinical trials and remains a preclinical biologic candidate.[1][2][3][4][5]

Other names

mesencephalic astrocyte-derived neurotrophic factorArginine-rich mutated in early stage of tumors