Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival
Open accessAbstract
Microglia and peripheral macrophages have both been implicated in amyotrophic lateral sclerosis (ALS), although their respective roles have yet to be determined. We now show that macrophages along peripheral motor neuron axons in mouse models and patients with ALS react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and depended on disease duration. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted differently to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a shift toward neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and may be of therapeutic value for ALS.
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In SOD1 mutant mice, reactive macrophages along peripheral axons of motor neurons were observed during disease progression.
“In SOD1 mutant mice, reactive macrophages along peripheral axons of motor neurons were observed during disease progression.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [364]
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Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
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- Authors
- Chiot, A., Zaïdi, S., Iltis, C., Ribon, M., Berriat, F., Schiaffino, L., Jolly, A., de la Grange, P., Mallat, M., Bohl, D., Millecamps, S., Seilhean, D., Lobsiger, C. S., & Boillée, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Verona (IT)
- Corresponding author
- Boillée, Séverine
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2020-10-19
- Volume
- 23
- Issue
- 11
- Pages
- 1339-1351
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W3093292900
- Cited by
- 122
- References
- 65
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 24 · 2023: 21 · 2022: 22 · 2021: 26 · 2020: 2
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-14-NEUR-0003, ANR-10-IAHU-0006)
- 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, peripheral macrophages, myeloid cell infiltration, reactive oxygen species, motor neuron axons, neuroinflammation, neurodegeneration, microglial activation, transcriptomics
- MeSH terms
- Adult, Aged, Amyotrophic Lateral Sclerosis, Animals, Axons, Female, Humans, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Motor Neurons, Sciatic Nerve, Spinal Cord, Microglia
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