2kve
C-terminal domain of mesencephalic astrocyte-derived neurotrophic factor (MANF)C-terminal domain of mesencephalic astrocyte-derived neurotrophic factor (MANF)
Structural highlights
DiseaseMANF_HUMAN Familial pancreatic carcinoma. FunctionMANF_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 PubMedMesencephalic 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
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