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

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

  • Brain Res. 2023 Feb 15:1801:148206. doi: 10.1016/j.brainres.2022.148206.
Yunzhu Yang 1,  Jiafa Zhang 2,  Canhong Yang 2,  Bo Dong 2,  Yanhong Fu 2,  Yuanyuan Wang 2,  Ming Gong 2,  Tao Liu 2,  Pingming Qiu 3,  Weibing Xie 3,  Tianming Lü 4
Affiliations

Affiliations

  • 1 Department of Neurology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China; Department of Neurology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou 341000, China.
  • 2 Department of Neurology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
  • 3 School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
  • 4 Department of Neurology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China. Electronic address: [email protected].
PMID: 36539049 DOI: 10.1016/j.brainres.2022.148206
Abstract

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.

Keywords

Alzheimer’s disease; Amyloid-beta; Autophagy; Microglia; Reactive oxygen species; Sulforaphane.

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