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Table 1 Human conditions with reported changes in MANF and CDNF expression
Disease Change Reference
Atrial fibrillation Decreased MANF mRNA and protein in serum Wang et al. 2020a
Diabetes type 1 Increased MANF protein in plasma Galli et al. 2016
Diabetes type 2 Increased MANF protein in plasma Wu et al. 2017; Fu et al. 2020
Fasting Increased MANF protein in plasma Galli et al. 2019a
Hepatocellular carcinoma Increased MANF mRNA and protein in tissue He et al. 2020a
Hyperlipidemia Increased MANF protein in serum Fu et al. 2020
Nonalcoholic steatohepatitis Decreased MANF protein in serum Sousa-Victor et al. 2019
Parkinson’s disease Increased MANF protein in plasma Galli et al. 2019b
Parkinson’s disease Increased CDNF protein in hippocampus Virachit et al. 2019
Physiological aging Decreased MANF protein in plasma Sousa-Victor et al. 2019
Polycystic ovary syndrome Decreased MANF protein in plasma Wei et al. 2020
Proliferative diabetic retinopathy Increased MANF protein in vitreous Gao et al. 2017
Retinal detachment Increased MANF protein in vitreous Gao et al. 2017
Rheumatoid arthritis Increased MANF mRNA in white blood cells Chen et al. 2015
Stroke Decreased CDNF mRNA levels in blood platelets Joshi et al. 2020
Systemic lupus erythematosus Increased MANF mRNA in white blood cells Chen et al. 2015
Table 2 Disease models in which MANF and CDNF were effective trophic factors
Disease Model system Species Reference
MANF
Alzheimer’s disease In vitro—challenging with amyloid β Human
(Neuro 2a and SH-SY5Y cell lines) Xu et al. 2019
Brain ischemia In vivo—distal middle cerebral artery occlusion (dMCAO) Rat Airavaara et al. 2009, Airavaara et al. 2010,Yang et al. 2014, Wang et al. 2016, Tseng et al. 2018,Mätlik et al. 2018, Gao et al. 2020
In vitro—tunicamycin treatment, oxygen-glucose deprivation Rat
(Primary neurons and primary astrocytes) Yu et al. 2010, Zhao et al. 2013
Cardiac ischemia/reperfusion
In vitro—simulated ischemia or tunicamycin treatment Rat Mouse (primary cardiac myocytes) Tadimalla et al. 2008, Arrieta et al. 2020
In vivo—coronary vessel occlusion Mouse Glembotski et al. 2012
Diabetes In vitro—challenge with cytokines Human (primary pancreatic islets) Hakonen et al. 2018, Cunha et al. 2017
In vitro —challenge with hyperglycemia Mouse (primary pancreatic islets) Danilova et al. 2019
Diabetic keratopathy In vivo—corneal epithelium wound healing model, diabetic and normoglycemic Mouse Wang et al. 2020a
Glaucoma In vivo—chronic ocular hypertension (COHT) model Rat Gao et al. 2017
Intracerebral hemorrhage In vivo—perforation model Rat Xu et al. 2018
Liver damage In vivo—aged mice Mouse Sousa-Victor et al. 2019
Liver steatosis In vitro—challenging with free fatty acids Human
(HepG2 cell line) He et al. 2020b
Myocardial infarction In vivo—coronary occlusion/reperfusion Mouse Glembotski et al. 2012
Nephrotic syndrome (Tg-C321R) In vitro Mouse (primary podocytes) Park et al. 2019
Parkinson’s disease In vivo—6-hydroxy dopamine (6-OHDA) Lesioning Rat, Mouse Voutilainen et al. 2009, Cordero-Llana et al. 2015
In vivo—1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning Mouse Liu et al. 2018b
In vitro—6-OHDA treatment Human (SH-SY5Y cell line) Zhang et al. 2017a
In vivo—6-OHDA treatment and α-synuclein overexpression Roundworm Zhang et al. 2018b
Retinal degeneration In vivo—5 klux light exposure Crxtvrm65 and Pde6bRd1 mutants, aged mice Mouse Neves et al. 2016,Neves et al. 2020
In vivo—rhodopsin S334ter mutation Rat Lu et al. 2018
Traumatic spinal cord injury In vivo—clip compressive crush injury Rat Gao et al. 2018
Traumatic brain injury In vivo—subarachnoid hemorrhage induction Rat Li et al. 2019
Disease Change Reference
Atrial fibrillation Decreased MANF mRNA and protein in serum Wang et al. 2020a
Diabetes type 1 Increased MANF protein in plasma Galli et al. 2016
Diabetes type 2 Increased MANF protein in plasma Wu et al. 2017; Fu et al. 2020
Fasting Increased MANF protein in plasma Galli et al. 2019a
Hepatocellular carcinoma Increased MANF mRNA and protein in tissue He et al. 2020a
Hyperlipidemia Increased MANF protein in serum Fu et al. 2020
Nonalcoholic steatohepatitis Decreased MANF protein in serum Sousa-Victor et al. 2019
Parkinson’s disease Increased MANF protein in plasma Galli et al. 2019b
Parkinson’s disease Increased CDNF protein in hippocampus Virachit et al. 2019
Physiological aging Decreased MANF protein in plasma Sousa-Victor et al. 2019
Polycystic ovary syndrome Decreased MANF protein in plasma Wei et al. 2020
Proliferative diabetic retinopathy Increased MANF protein in vitreous Gao et al. 2017
Retinal detachment Increased MANF protein in vitreous Gao et al. 2017
Rheumatoid arthritis Increased MANF mRNA in white blood cells Chen et al. 2015
Stroke Decreased CDNF mRNA levels in blood platelets Joshi et al. 2020
Systemic lupus erythematosus Increased MANF mRNA in white blood cells Chen et al. 2015
Table 2 Disease models in which MANF and CDNF were effective trophic factors
Disease Model system Species Reference
MANF
Alzheimer’s disease In vitro—challenging with amyloid β Human
(Neuro 2a and SH-SY5Y cell lines) Xu et al. 2019
Brain ischemia In vivo—distal middle cerebral artery occlusion (dMCAO) Rat Airavaara et al. 2009, Airavaara et al. 2010,Yang et al. 2014, Wang et al. 2016, Tseng et al. 2018,Mätlik et al. 2018, Gao et al. 2020
In vitro—tunicamycin treatment, oxygen-glucose deprivation Rat
(Primary neurons and primary astrocytes) Yu et al. 2010, Zhao et al. 2013
Cardiac ischemia/reperfusion
In vitro—simulated ischemia or tunicamycin treatment Rat Mouse (primary cardiac myocytes) Tadimalla et al. 2008, Arrieta et al. 2020
In vivo—coronary vessel occlusion Mouse Glembotski et al. 2012
Diabetes In vitro—challenge with cytokines Human (primary pancreatic islets) Hakonen et al. 2018, Cunha et al. 2017
In vitro —challenge with hyperglycemia Mouse (primary pancreatic islets) Danilova et al. 2019
Diabetic keratopathy In vivo—corneal epithelium wound healing model, diabetic and normoglycemic Mouse Wang et al. 2020a
Glaucoma In vivo—chronic ocular hypertension (COHT) model Rat Gao et al. 2017
Intracerebral hemorrhage In vivo—perforation model Rat Xu et al. 2018
Liver damage In vivo—aged mice Mouse Sousa-Victor et al. 2019
Liver steatosis In vitro—challenging with free fatty acids Human
(HepG2 cell line) He et al. 2020b
Myocardial infarction In vivo—coronary occlusion/reperfusion Mouse Glembotski et al. 2012
Nephrotic syndrome (Tg-C321R) In vitro Mouse (primary podocytes) Park et al. 2019
Parkinson’s disease In vivo—6-hydroxy dopamine (6-OHDA) Lesioning Rat, Mouse Voutilainen et al. 2009, Cordero-Llana et al. 2015
In vivo—1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning Mouse Liu et al. 2018b
In vitro—6-OHDA treatment Human (SH-SY5Y cell line) Zhang et al. 2017a
In vivo—6-OHDA treatment and α-synuclein overexpression Roundworm Zhang et al. 2018b
Retinal degeneration In vivo—5 klux light exposure Crxtvrm65 and Pde6bRd1 mutants, aged mice Mouse Neves et al. 2016,Neves et al. 2020
In vivo—rhodopsin S334ter mutation Rat Lu et al. 2018
Traumatic spinal cord injury In vivo—clip compressive crush injury Rat Gao et al. 2018
Traumatic brain injury In vivo—subarachnoid hemorrhage induction Rat Li et al. 2019
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