Microglial cells are the major immune cells of the central nervous system (CNS), and directly react to neurodegeneration, but other immune cell types are also able to react to pathology and can modify the course of neurodegenerative processes. These mainly include monocytes/macrophages and lymphocytes. While these peripheral immune cells were initially considered to act only after infiltrating the CNS, recent evidence suggests that some of them can also act directly from the periphery. We will review the existing and emerging evidence for a role of peripheral immune cells in neurodegenerative diseases, both with and without CNS infiltration. Our focus will be on amyotrophic lateral sclerosis, but we will also compare to Alzheimer’s disease and Parkinson’s disease to highlight similarities or differences. Peripheral immune cells are easily accessible, and therefore may be an attractive therapeutic target for neurodegenerative diseases. Thus, understanding how these peripheral immune cells communicate with the CNS deserves deeper investigation.
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The author’s research is supported by grants from the Fondation pour la Recherche Médicale (FRM, Equipe FRM EQU202103012581), the ALS association (ALSA, 20-IIA-530), NRJ-Institut de France, Fondation Thierry Latran, l’ARMC, S.L.A.F.R., ‘La longue route des malades de la SLA’, ‘Un pied devant l’autre’, Ferblanc and private donors to ALS at the ICM. F.B. was supported by a fellowship from the French ministry of research. We thank M. Mallat for helpful comments. Figures were partly drawn with free-to-use Servier Medical Art images available at https://smart.servier.com/.
The authors declare no competing interests.
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Berriat, F., Lobsiger, C.S. & Boillée, S. The contribution of the peripheral immune system to neurodegeneration. Nat Neurosci (2023). https://doi.org/10.1038/s41593-023-01323-6