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Cited by 164Amyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research Studies

The microglial component of amyotrophic lateral sclerosis

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Clarke, Benjamin E, Patani, Rickie·2020·Brain
DOI 10.1093/brain/awaa309PMC PMC7805793
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Abstract

Microglia are the primary immune cells of the CNS, carrying out key homeostatic roles and undergoing context-dependent and temporally regulated changes in response to injury and neurodegenerative diseases. Microglia have been implicated in playing a role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by extensive motor neuron loss leading to paralysis and premature death. However, as the pathomechansims of ALS are increasingly recognized to involve a multitude of different cell types, it has been difficult to delineate the specific contribution of microglia to disease. Here, we review the literature of microglial involvement in ALS and discuss the evidence for the neurotoxic and neuroprotective pathways that have been attributed to microglia in this disease. We also discuss accumulating evidence for spatiotemporal regulation of microglial activation in this context. A deeper understanding of the role of microglia in the 'cellular phase' of ALS is crucial in the development of mechanistically rationalized therapies.

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  • Progression of TDP-43 proteinopathies involves non-cell-autonomous signaling among multiple cell types, including astrocytes, microglia, and neurons.

    “Progression of TDP-43 proteinopathies involves non-cell-autonomous signaling among multiple cell types, including astrocytes, microglia, and neurons (Clarke & Patani 2020, Izrael et al. 2020, Vahsen et al. 2021).”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Clarke & Patani 2020

    The TARDBP section describes interactions between neuronal TDP-43 and microglia in an ALS mouse model. The ‘Microglial interactions with other cell types in ALS > Astrocytes’ section describes astrocyte–microglia crosstalk and non-cell-autonomous motor-neuron death in ALS, but its specific examples concern SOD1 models, not TDP-43 proteinopathies. The source therefore supports the cellular-interaction premise, but not the claim that signaling among all three cell types drives progression of TDP-43 proteinopathies generally. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Clarke, B. E., & Patani, R.
Affiliations
The Francis Crick Institute (GB)
Corresponding author
Patani, Rickie
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2020-12-01
Volume
143
Issue
12
Pages
3526-3539
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awaa309
PMC
PMC7805793
OpenAlex
W3108677428
Cited by
164
References
36
Citations by year
2026: 26 · 2025: 41 · 2024: 32 · 2023: 28 · 2022: 24 · 2021: 12 · 2020: 1
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Francis Crick Institute
  • Cancer Research UK (FC0101 10)
  • UK Medical Research Council (FC010110)
  • WellcomeTrust (FC010110)
  • MRC Senior Clinical Fellowship (MR/S006591/1)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
amyotrophic lateral sclerosis, microglia, neuroinflammation, microglial activation, neurotoxicity, neuroprotection, motor neuron degeneration, neurodegeneration, spatiotemporal control, ALS pathogenesis, ALS therapy
MeSH terms
Amyotrophic Lateral Sclerosis, Humans, Microglia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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