Trophic activities of endoplasmic reticulum proteins CDNF and MANF.

摘要: Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine (CDNF) are endoplasmic reticulum (ER) luminal proteins that confer trophic activities in a wide range of tissues under diverse pathological conditions. Despite initially being classified as factors, neither protein structurally nor functionally resembles bona fide factors. Their highly homologous structures comprise unique globular, saposin-like domain within the N-terminus joined by flexible linker to C-terminus containing SAP-like domain, CXXC motif an ER retention sequence. Neurotrophic factors exert effects binding cognate receptors plasma membrane; however, no cell surface have been identified for MANF CDNF. Both can act unfolded response (UPR) genes modulate UPR inflammatory processes. The activity CDNF extends beyond central nervous system with crucial development pancreatic β cells both variety diseases related liver, heart, skeletal tissue, kidney peripheral system. In this article, features CDNF, such their structure mechanisms action stress inflammation, will be reviewed. Recently interactions lipids membrane trafficking also described. Lastly, function therapeutic potential different including recent clinical trial using treat Parkinson's disease discussed. Collectively, review highlight broad-acting regulate functions reticulum.