Fig. 6

Proposed inflammasome activation mechanisms with Aβ and MAC in RPE/choroid. Age-associated changes in RPE/choroid include an increased accumulation of Aβ that acts as a “Signal 1” to activate the NF-κB pathway (1). This upregulates the transcription of NLRP3, pro-IL-18 and pro-IL-1β (2). Next, assembly and activation of the NLRP3 inflammasome is triggered by MAC deposition (“Signal 2”) on the RPE cell membrane (3). NLRP3 activation results in pro-caspase-1 auto-cleavage (4). The cleaved caspase-1 then functions as a cytokine-processing enzyme to facilitate the production and secretion of active, mature IL-18 and IL-1β (5). ATAC compound works as a MAC inhibitor, suppressing MAC-induced inflammasome activation on RPE