Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5684940 | Translational Research | 2017 | 24 Pages |
Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages. The cytoprotective mechanisms of MANF on ER stress are currently under active investigation. In addition, for the first time, we have discovered that MANF can potentially serve as a urinary ER stress biomarker in ER stress-mediated kidney disease. These studies have underscored the diagnostic and therapeutic importance of MANF in ER diseases.
Keywords
6-OHDACDNFATF6PDGFThapsigarginT1DIRE1UPRtunicamycinXBP1SAAVERSEMCAOMesencephalic astrocyte-derived neurotrophic factorGDNFInositol-requiring enzyme-1KDEL receptorSCGKDELRSCASAP domain6-HydroxydopamineER stress response elementLAMB2SI/RTBPAKINODnuclear magnetic resonanceBiPC/EBP homologous proteinsuperior cervical ganglionI/RMAPKPKR-like ER kinasespinocerebellar ataxiaacute kidney injuryMyocardial infarctionmiddle cerebral artery occlusionischemia/reperfusionSimulated ischemiaParkinson's diseaseNMRsubstantia nigraCHOPDiabetes mellitusType 1 diabetesNonobese diabeticARMETnephrotic syndromeendoplasmic reticulumplatelet-derived growth factorglial cell line–derived neurotrophic factoractivating transcription factor 6MANFAdeno-associated virusER stress responseUnfolded protein responsemitogen-activated protein kinasePERK
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Authors
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen,