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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS/FTD

Fig. 3

Overview of the neuroinflammatory pathways at play in C9-ALS/FTD. Coinciding with the neurodegeneration, astrocytes and microglia undergo a switch towards a neurotoxic and (over)activated state in which they produce and secrete an array of pro-inflammatory factors including cytokines (TNFα, IL-6, IL-12, IL-1β, TGFβ, IFNγ), glutamate, NO and ROS. During disease progression, peripheral immune cells such as T cells, B cells, monocytes and NK cells migrate into the CNS. Upon CNS infiltration, monocytes may differentiate to macrophages that act similar to the CNS-residing microglia. Although an active involvement of T cells in ALS pathophysiology is debated, disease progression has been associated with a disbalance between neuroprotective and neurotoxic T cell populations. Next, NK cells are attracted to the CNS by chemokines and can stimulate neurotoxic glia differentiation or directly be toxic to the neurons. Finally, although their role has never been directly demonstrated, activated B cells may exert toxicity by the secretion of autoimmune antibodies. CCL2: C–C motif chemokine ligand 2; CNS, central nervous system; CX3CL1: CX3 chemokine ligand 1; CXCL10: C-X-C motif ligand 10; IFNγ, interferon γ; IL, interleukin; NK cell: natural killer cell; NO, nitric oxide; ROS, reactive oxygen species; TGFβ, transforming growth factor β; TNFα, tumor necrosis factor α

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