Evidence map›Paper›PMID 33296727›Full record

ArticleNeurobiology of disease2021

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

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

Open access · goldAbstract read
In one paragraph

Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 47 citations in OpenAlex.

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  12. AβJournal of molecular histology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Yongchao WangDepartment of Cell and Development Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States of America.
Wen WenDepartment of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States of America.
Hui LiDepartment of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States of America.
Marco ClementinoDepartment of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, United States of America.
Hong XuDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States of America.
Mei XuDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States of America.
Murong MaDepartment of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States of America.
Jacqueline FrankDepartment of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, United States of America.
Jia LuoDepartment of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States of America; Iowa City VA Health Care System, Iowa City, IA 52246, United States of America. Electronic address: jia-luo@uiowa.edu.
University of Kentucky · USUniversity of Iowa · USIowa City VA Health Care System · USVanderbilt University · US

Funding

GSK3BETA, A MEDIATOR OF ETHANOL NEUROTOXICITYR01AA015407 · NIAAA · WEST VIRGINIA UNIVERSITY · PI JIA LUO · 2005 to 2026
$6.2M
ALCOHOL AND BREAST CANCERR01AA017226 · NIAAA · WEST VIRGINIA UNIVERSITY · PI LUO, JIA · 2008 to 2024
$5.2M
TRAINING PROGRAM IN OXIDATIVE STRESS AND NUTRITIONT32DK007778 · NIDDK · UNIVERSITY OF KENTUCKY · PI WEBB, NANCY R · 2000 to 2019
$2.5M
Thiamine deficiency and alcohol-induced neurodegenerationI01BX001721 · VA · VA MEDICAL CENTER - LEXINGTON, KY · PI LUO, JIA · 2014 to 2022
–
BLRD VA I01 BX001721NIAAA NIH HHS R01 AA015407NIAAA NIH HHS R01 AA017226NIDDK NIH HHS T32 DK007778
6 · The paper itself

Abstract

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in ethanol-induced neurodegeneration and its association with ER stress regulation, we established a CNS-specific Manf knockout mouse model and examined the effects of MANF deficiency on ethanol-induced neuronal apoptosis and ER stress using a third-trimester equivalent mouse model. We found MANF deficiency exacerbated ethanol-induced neuronal apoptosis and ER stress and that blocking ER stress abrogated the harmful effects of MANF deficiency on ethanol-induced neuronal apoptosis. Moreover, using an animal model of ER-stress-induced neurodegeneration, we demonstrated that MANF deficiency potentiated tunicamycin (TM)-induced ER stress and neurodegeneration. A whole transcriptome RNA sequencing also supported the functionality of MANF in ER stress modulation and revealed targets that may mediate the ER stress-buffering capacity of MANF. Collectively, these results suggest that MANF is a neurotrophic factor that can protect neurons against ethanol-induced neurodegeneration by ameliorating ER stress.

Indexed as

AnimalsApoptosisCentral Nervous System DepressantsEndoplasmic Reticulum StressEthanolFemaleFetal Alcohol Spectrum DisordersMiceMice, KnockoutNerve Growth FactorsNeuronsNeuroprotectionPregnancyPregnancy Trimester, ThirdTunicamycinUnfolded Protein ResponseCentral Nervous System DepressantsEthanolMANF protein, mouseNerve Growth FactorsTunicamycinAlcohol abuseApoptosisBrainDevelopmentUnfolded protein response

Identifiers

PMID33296727
PMCPMC7856049
OpenAlexW3112749838

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.