1. Academic Validation
  2. Ginkgolide B inactivates the NLRP3 inflammasome by promoting autophagic degradation to improve learning and memory impairment in Alzheimer's disease

Ginkgolide B inactivates the NLRP3 inflammasome by promoting autophagic degradation to improve learning and memory impairment in Alzheimer's disease

  • Metab Brain Dis. 2022 Feb;37(2):329-341. doi: 10.1007/s11011-021-00886-2.
Li Shao 1 2 Chen Dong 3 Deqin Geng 4 5 Qing He 2 Yu Shi 6
Affiliations

Affiliations

  • 1 The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China.
  • 2 Department of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221116, People's Republic of China.
  • 3 Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
  • 4 The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China. geng_deqin@163.com.
  • 5 Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, Jiangsu, 221002, People's Republic of China. geng_deqin@163.com.
  • 6 Department of Neurology, Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou, Jiangsu, 221005, People's Republic of China.
Abstract

The NLR family, pyrin domain containing 3 (NLRP3) inflammasome drives the progression of Alzheimer's disease (AD). Ginkgolide B (GB) is a potential anti-inflammatory compound that controls neuro-inflammation. The aim of this study was to evaluate the effect of GB on the NLRP3 inflammasome in AD. The effect of GB on the conversion between the M1 and M2 microglial phenotype was examined using quantitative Real-Time PCR and immunostaining. Western blotting assays and ELISA were used to detect changes in neuro-inflammation following GB treatment, including the NLRP3 inflammasome pathway and Autophagy. In order to evaluate the cognitive function of male senescence-accelerated mouse prone 8 (SAMP8) mice, behavioral tests, including the Morris water maze and novel object recognition tests, were performed. GB significantly decreased the intracellular pro-inflammatory cytokine levels in lipopolysaccharide-treated BV2 cells and improved cognitive behavior in SAMP8 mice. Moreover, GB deactivated the NLRP3 inflammasome, and this effect was dependent on Autophagy. Ubiquitination was associated with GB-induced autophagic NLRP3 degradation. These results were further validated in the hippocampus of SAMP8 mice. Thus, GB exerted a neuroprotective effect on the cognitive function of SAMP8 mice by suppressing the activation of NLRP3 inflammasome via autophagic degradation.

Keywords

Alzheimer’s disease; Autophagy; Ginkgolide B; NLRP3 inflammasome; Ubiquitination.

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