Fig. (1) Schematic description of inflammasome activation pathways in neurodegenerative disorders. The assembly of the NLRP3 inflammasome in CNS inflammatory cells can be induced by fibrillar amyloid β (Aβ) in Alzheimer’s disease or fibrillar α-synuclein (α-Syn) in Parkinson’s disease. Phagocytosis of fibrillar Aβ induces lysosomal rupture, resulting in the leakage of cathepsin B. Phagocytosis of fibrillar α-Syn also leads to the release of cathepsin B. Cytoplasmic cathepsin B activate the NLRP3 inflammasome. IL-1β and IL-18 can promote polarization of helper T (Th) cells. Cytokines released by both Th1 and Th17 induce the inflammatory reactions, which promote demyelination and axonal damage in the multiple sclerosis. In amyotrophic lateral sclerosis, the interaction of TAR DNA binding protein (TDP-43) with CD14 receptor promotes the activation of nuclear factor κB (NF-κB) pathways, leading to the increased expression of NLRP3 mRNA and production of caspase-1 and IL-1β.

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