title: Antimalarial drug artemisinin extenuates amyloidogenesis and neuroinflammation in APPswe/PS1dE9 transgenic mice via inhibition of nuclear factor-κB and NLRP3 inflammasome activation.
abstract: BACKGROUND
  The activation of nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome is involved in neuroinflammation, which is closely linked to Alzheimer's disease (AD). In vivo and in vitro studies have suggested that artemisinin shows antiinflammatory effects in inflammation-related diseases. However, the impacts of artemisinin on AD have not been investigated.
  
  
  OBJECTIVE
  In this study, 5-month-old APPswe/PS1dE9 transgenic mice were treated daily with 40 mg/kg artemisinin for 30 days by intraperitoneal injection to evaluate the effects of artemisinin on AD.
  
  
  RESULTS
  We found that artemisinin treatment (1) decreased neuritic plaque burden; (2) did not alter Aβ transport across the blood-brain barrier; (3) regulated APP processing via inhibiting β-secretase activity; (4) inhibited NF-κB activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice.
  
  
  CONCLUSIONS
  The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathology due to its effects on suppressing NF-κB activity and NALP3 inflammasome activation. Our study suggests that targeting NF-κB activity and NALP3 inflammasome activation offers a valuable intervention for AD.
authors: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Jian-Quan
authors: JQ
authors: Shi
authors: Chu-Chu
authors: CC
authors: Zhang
authors: Xiu-Lan
authors: XL
authors: Sun
authors: Xin-Xin
authors: XX
authors: Cheng
authors: Jiang-Bo
authors: JB
authors: Wang
authors: Ying-Dong
authors: YD
authors: Zhang
authors: Jun
authors: J
authors: Xu
authors: Hai-Qiang
authors: HQ
authors: Zou
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053764:Presenilin-1 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D000962:Antimalarials; D037621:Artemisinins; D002352:Carrier Proteins; D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053764:Presenilin-1; C031327:artemisinin