FIGURE 3.

The ASC speck directly and indirectly contributes to the accumulation and spreading of AD/PD related misfolded protein aggregates via several mechanisms. The ASC speck can directly cross-seed the aggregation of Aβ by serving as a molecular scaffold for aggregation (top left). Caspase-1, the effector component of the inflammasome/ASC speck, can directly cleave tau and α-syn monomers into a pro-aggregatory form for seeding nucleation (top right). IL-1β, the downstream product of the ASC speck, can act as a cellular signal to upregulate key enzymes for the pro-aggregatory PTMs of tau and α-syn (bottom left). The ASC speck contributes to the dysregulation of protective disease-associated microglia (DAMs) and subsequent skewed pro-inflammatory phenotype resulting in a decrease in phagocytic clearance of AD/PD related misfolded protein aggregates (bottom right).