MANF is neuroprotective against ethanol-induced neurodegeneration through ameliorating ER stress

Wang, Yongchao; Wen, Wen; Li, Hui; Clementino, Marco; Xu, Hong; Xu, Mei; Ma, Murong; Frank, Jacqueline A.; Luo, Jia

doi:10.1016/j.nbd.2020.105216

Cited by 27 publications

(22 citation statements)

References 58 publications

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“…Further research on the exact mechanisms of α-syn clearance will help understand the neuroprotective role of IRE1. Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as ARMET (arginine-rich mutated in early-stage tumors) is present in ER and promotes neuronal cell survival through UPR regulation (Apostolou et al, 2008;Renko et al, 2018;Wang et al, 2021). ER stress triggers the accumulation of misfolded α-syn (Colla et al, 2012a).…”

Section: Mechanism Of Neuronal Clearance Of Misfolded α-Synuclein By Autophagymentioning

confidence: 99%

“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease

Ray

Mahalakshmi

Tuladhar

et al. 2021

Front. Cell Dev. Biol.

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Parkinson’s disease (PD) is a pathological condition characterized by the aggregation and the resultant presence of intraneuronal inclusions termed Lewy bodies (LBs) and Lewy neurites which are mainly composed of fibrillar α-synuclein (α-syn) protein. Pathogenic aggregation of α-syn is identified as the major cause of LBs deposition. Several mutations in α-syn showing varied aggregation kinetics in comparison to the wild type (WT) α-syn are reported in PD (A30P, E46K, H 50Q, G51D, A53E, and A53T). Also, the cell-to-cell spread of pathological α-syn plays a significant role in PD development. Interestingly, it has also been suggested that the pathology of PD may begin in the gastrointestinal tract and spread via the vagus nerve (VN) to brain proposing the gut–brain axis of α-syn pathology in PD. Despite multiple efforts, the behavior and functions of this protein in normal and pathological states (specifically in PD) is far from understood. Furthermore, the etiological factors responsible for triggering aggregation of this protein remain elusive. This review is an attempt to collate and present latest information on α-syn in relation to its structure, biochemistry and biophysics of aggregation in PD. Current advances in therapeutic efforts toward clearing the pathogenic α-syn via autophagy/lysosomal flux are also reviewed and reported.

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Section: Mechanism Of Neuronal Clearance Of Misfolded α-Synuclein By Autophagymentioning

confidence: 99%

“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease

Ray

Mahalakshmi

Tuladhar

et al. 2021

Front. Cell Dev. Biol.

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“…MANF is an ER-stress-inducible secretory protein expressed in many human and mouse tissues, with a particularly high expression level in secretory tissues such as the pancreas [ 286 , 287 ]. MANF is activated by alcohol exposure and plays a protective role by alleviating alcohol-induced ER stress in the brain and in cultured acinar cells [ 210 , 224 , 288 ] ( Figure 3 ). The cytoprotective role of MANF in the pancreas has been demonstrated by the increased apoptosis and reduced proliferation of pancreatic beta cells and an insulin-deficient phenotype in pancreatic MANF knockout mice [ 289 , 290 ].…”

Section: Potential Treatment Of Alcoholic Pancreatitis By Targeting Er Stress and Uprmentioning

confidence: 99%

Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Wen

Luo

2022

Biomedicines

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Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.

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“…MANF is an ER stress-inducible secretory protein expressed in many human and mouse tissues, with a particularly high expression level in secretory tissues such as the pancreas 286,287 . MANF is activated by alcohol exposure and plays a protective role by alleviating alcohol-induced ER stress in the brain and in cultured acinar cells 199,229,288 (Fig. 3).…”

Section: Potential Treatment Of Alcoholic Pancreatitis By Targeting Er Stress and Uprmentioning

confidence: 99%

Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Li¹,

Wen²,

Luo³

2021

Preprint

Self Cite

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Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

show abstract

MANF is neuroprotective against ethanol-induced neurodegeneration through ameliorating ER stress

Cited by 27 publications

References 58 publications

“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease

“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease

Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

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