Structural highlights
Disease
[MANF_HUMAN] Familial pancreatic carcinoma.
Function
[MANF_HUMAN] Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. 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.[1] [2]
Publication Abstract from PubMed
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson's disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well-known inhibitor of pro-apoptotic Bcl-2-associated X protein (Bax). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.
Neurotrophic factor MANF has a unique mechanism to rescue apoptotic neurons.,Hellman M, Arumae U, Yu LY, Lindholm P, Peranen J, Saarma M, Permi P J Biol Chem. 2010 Nov 3. PMID:21047780[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Petrova P, Raibekas A, Pevsner J, Vigo N, Anafi M, Moore MK, Peaire AE, Shridhar V, Smith DI, Kelly J, Durocher Y, Commissiong JW. MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J Mol Neurosci. 2003 Apr;20(2):173-88. PMID:12794311
- ↑ Apostolou A, Shen Y, Liang Y, Luo J, Fang S. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res. 2008 Aug 1;314(13):2454-67. doi: 10.1016/j.yexcr.2008.05.001. Epub , 2008 May 13. PMID:18561914 doi:http://dx.doi.org/10.1016/j.yexcr.2008.05.001
- ↑ Hellman M, Arumae U, Yu LY, Lindholm P, Peranen J, Saarma M, Permi P. Neurotrophic factor MANF has a unique mechanism to rescue apoptotic neurons. J Biol Chem. 2010 Nov 3. PMID:21047780 doi:10.1074/jbc.M110.146738
