Sulforaphane attenuates microglia-mediated neuronal damage by down-regulating the ROS/autophagy/NLRP3 signal axis in fibrillar Aβ-activated microglia

The neuroinflammatory hypothesis of Alzheimer's disease (AD) posits that amyloid-beta (Aβ) phagocytosis along with subsequent lysosomal damage and NLRP3 inflammasome activation plays important roles in Aβ-induced microglia activation and microglia-induced neurotoxicity. Sulforaphane (SFN) has neuroprotective effects for AD. However, whether SFN can inhibit its cytotoxic autophagy and NLRP3 inflammasome activation in microglia remain unknown. In this study, results showed SFN played an indirect, protective role on neurons via a series of impacts on Aβ-activated microglia, including inhibition of autophagy initiation as well as autophagic lysosomal membrane permeability and subsequent NLRP3/caspase-1 inflammasomes activation. M1 phenotype polarization was also inhibited. Our results demonstrated that SFN could inhibit the cytostatic autophagy-induced NLRP3 signaling pathway in Aβ-activated microglia by decreasing reactive oxygen species (ROS) production. These results provide novel insight into the potential role of SFN in AD therapy.