期刊
NATURE NEUROSCIENCE
卷 23, 期 11, 页码 1339-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41593-020-00718-z
关键词
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资金
- program Investissements d'avenir [ANR-10-IAIHU-06]
- Thierry Latran foundation
- NRJ-Institut de France
- European FP7 International Reintegration Marie Curie Grant [IRG230978]
- ERANET-NEURON (TracInflam) [ANR-14-NEUR-0003-02]
- ALS association (ALSA) [16-IIP-258, 20-IIA-530]
- associations Aide a la Recherche des Maladies du Cerveau (ARMC)
- La longue route des malades de la SLA
- SLAFR
- un pied devant l'autre
- French ministry of research
- Association pour la Recherche sur la Sclerose Laterale Amyotrophique et autres Maladies du Motoneurone (ARSLA)
Peripheral macrophages located along motor axons react differently to neurodegeneration compared to CNS microglia in ALS mice. Modifying peripheral macrophages suppresses proinflammatory microglial responses, shifting them toward neuronal support. 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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