Mesencephalic astrocyte-derived neurotrophic factor

Definition:

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells. Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions.

References:

[1]. Meirong Bai, et al. Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection. Nat Commun. 2018 Mar 1;9(1):897. [Content Brief]

[2]. Andria Apostolou, et al. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res. 2008 Aug 1;314(13):2454-67. [Content Brief]

[3]. Penka Petrova, et al. MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J Mol Neurosci. 2003 Apr;20(2):173-88. [Content Brief]

[4]. Christopher C Glembotski, et al. Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion. J Biol Chem. 2012 Jul 27;287(31):25893-904. [Content Brief]

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