Evidence map›Paper›PMID 34057020›Full record

ReviewAutophagy2022

Autophagy and ALS: mechanistic insights and therapeutic implications.

Jason P Chua, Hortense De Calbiac, Edor Kabashi, Sami J Barmada

Open access · bronzeAbstract readReview
In one paragraph

Review in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
13.0field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 171 citations in OpenAlex.

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46 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 2 countries.

Jason P ChuaDepartment of Neurology, University of Michigan, Ann Arbor, MI, United States.ORCID 0000-0003-4514-1491
Hortense De CalbiacRecherche translationnelle sur les maladies neurologiques, Institut Imagine, UMR-1163 INSERM et Université Paris Descartes, Hôpital Universitaire Necker-Enfants Malades, Paris, France.ORCID 0000-0002-6246-0833
Edor KabashiRecherche translationnelle sur les maladies neurologiques, Institut Imagine, UMR-1163 INSERM et Université Paris Descartes, Hôpital Universitaire Necker-Enfants Malades, Paris, France.ORCID 0000-0003-4118-251X
Sami J BarmadaDepartment of Neurology, University of Michigan, Ann Arbor, MI, United States.ORCID 0000-0002-9604-968X
Inserm · FRUniversity of Michigan · US

Funding

Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DOUGLAS C NOLL · 2021 to 2026
$26.5M
Michigan Alzheimer's Disease Core CenterP30AG053760 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALBIN, ROGER L · 2016 to 2020
$10.1M
RNA decay in amyotrophic lateral sclerosis and frontotemporal lobar degenerationR01NS097542 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2016 to 2025
$3.8M
UM Clinical Neuroscientist Training ProgramR25NS089450 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALBIN, ROGER L · 2014 to 2023
$1.3M
NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG072931NINDS NIH HHS R01 NS097542NINDS NIH HHS R25 NS089450
6 · The paper itself

Abstract

Mechanisms of protein homeostasis are crucial for overseeing the clearance of misfolded and toxic proteins over the lifetime of an organism, thereby ensuring the health of neurons and other cells of the central nervous system. The highly conserved pathway of autophagy is particularly necessary for preventing and counteracting pathogenic insults that may lead to neurodegeneration. In line with this, mutations in genes that encode essential autophagy factors result in impaired autophagy and lead to neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). However, the mechanistic details underlying the neuroprotective role of autophagy, neuronal resistance to autophagy induction, and the neuron-specific effects of autophagy-impairing mutations remain incompletely defined. Further, the manner and extent to which non-cell autonomous effects of autophagy dysfunction contribute to ALS pathogenesis are not fully understood. Here, we review the current understanding of the interplay between autophagy and ALS pathogenesis by providing an overview of critical steps in the autophagy pathway, with special focus on pivotal factors impaired by ALS-causing mutations, their physiologic effects on autophagy in disease models, and the cell type-specific mechanisms regulating autophagy in non-neuronal cells which, when impaired, can contribute to neurodegeneration. This review thereby provides a framework not only to guide further investigations of neuronal autophagy but also to refine therapeutic strategies for ALS and related neurodegenerative diseases.

Indexed as

Amyotrophic Lateral SclerosisFrontotemporal DementiaAutophagyHumansProteostasisUnfolded Protein ResponseAmyotrophic lateral sclerosisC9orf72CHMP2Bmacroautophagymitophagymyelinophagyneuronal autophagyoptineurinSQSTM1/p62TBK1

Identifiers

PMID34057020
PMCPMC8942428
OpenAlexW3164735937

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.