Fig. 9.

Schematic presentation of NLRP3 inflammasome activation-induced pyroptosis and neuroinflammation in pre-symptomatic stage during ALS progression. From pre-symptomatic stage of ALS, cellular aberrant mSOD1 participates in assemble of NLRP3 inflammasome, which in turn activates pro-caspase-1. Active caspase-1 not only promotes the maturation of IL-1β, but also cleaves GSDMD, releasing its N-terminal fragment. Then these N-terminal fragment translocate to the plasma membrane causing pore formation and inducing pyroptosis. IL-1β released by degenerated motor neurons leads to continuously activate of astrocytes and microglia, which aggravates neuroinflammation, and participates in the progression of ALS