Non-neuronal cells in amyotrophic lateral sclerosis — from pathogenesis to biomarkers
Abstract
The prevailing motor neuron-centric view of amyotrophic lateral sclerosis (ALS) pathogenesis could be an important factor in the failure to identify disease-modifying therapy for this neurodegenerative disorder. Non-neuronal cells have crucial homeostatic functions within the CNS and evidence of involvement of these cells in the pathophysiology of several neurodegenerative disorders, including ALS, is accumulating. Microglia and astrocytes, in crosstalk with peripheral immune cells, can exert both neuroprotective and adverse effects, resulting in a highly nuanced range of neuronal and non-neuronal cell interactions. This Review provides an overview of the diverse roles of non-neuronal cells in relation to the pathogenesis of ALS and the emerging potential of non-neuronal cell biomarkers to advance therapeutic development.
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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 Vahsen et al. 2021
The TDP-43 models section (pp. 13, 20) describes microglia-dependent toxicity in co-culture and progressive non-cell-autonomous motor-neuron loss in rats expressing mutant TDP-43 in astrocytes, accompanied by microglial activation. It also says whether microglia actively contribute to disease pathogenesis or merely respond to neuronal damage remains unresolved. These ALS-model findings support interactions among the named cell types, but not the broader assertion that signaling among all three drives progression of TDP-43 proteinopathies generally. (LLM, conf=0.83)
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References 220 · Cited by 147
Research works printed but not linked: 6
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- Authors
- Vahsen, B. F., Gray, E., Thompson, A. G., Ansorge, O., Anthony, D. C., Cowley, S. A., Talbot, K., & Turner, M. R.
- Affiliations
- John Radcliffe Hospital (GB)
- University of Oxford (GB)
- Corresponding author
- Talbot, Kevin
- Turner, Martin R.
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2021-04-29
- Volume
- 17
- Issue
- 6
- Pages
- 333-348
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W3158984109
- Cited by
- 147
- References
- 220
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 34 · 2023: 32 · 2022: 30 · 2021: 11
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (NIHR-INF-1363)
- Motor Neurone Disease Association (Thompson/Jan20/952‐795, TURNER/OCT18/989-797)
- Medical Research Council (MR/L023784/2, MR/M024962/1, 2283992, MR/T006927/1, MC_EX_MR/N50192X/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, non-neuronal cells, microglia, astrocytes, oligodendrocytes, neuroinflammation, peripheral immune cells, disease-modifying therapy, biomarkers, ALS pathogenesis, neurodegeneration
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Astrocytes, DNA-Binding Proteins, Humans, Motor Neurons, Biomarkers, Microglia
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