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Publication : Blocking immune cell infiltration of the central nervous system to tame Neuroinflammation in Amyotrophic lateral sclerosis.

First Author  Garofalo S Year  2022
Journal  Brain Behav Immun Volume  105
Pages  1-14 PubMed ID  35688338
Mgi Jnum  J:355734 Mgi Id  MGI:7311365
Doi  10.1016/j.bbi.2022.06.004 Citation  Garofalo S, et al. (2022) Blocking immune cell infiltration of the central nervous system to tame Neuroinflammation in Amyotrophic lateral sclerosis. Brain Behav Immun 105:1-14
abstractText  Neuroinflammation is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, peripheral immune cells were discovered as pivotal players that promptly participate in this process, speeding up neurodegeneration during progression of the disease. In particular, infiltrating T cells and natural killer cells release inflammatory cytokines that switch glial cells toward a pro-inflammatory/detrimental phenotype, and directly attack motor neurons with specific ligand-receptor signals. Here, we assessed the presence of lymphocytes in the spinal cord of sporadic ALS patients. Furthermore, we demonstrate that blocking the extravasation of immune cells in the central nervous system using Natalizumab (NAT), an antibody for the alpha4 integrin, reduces the level of interferon-gamma in the spinal cord of ALS mouse models, such as the hSOD1(G93A) and TDP43(A315T) mice, modifying microglia and astrocytes phenotype, increasing motor neuron number and prolonging the survival time. Taken together, our results establish a central role for the immune cells as drivers of inflammation in ALS.
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