Antimalarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/PS1dE9 Transgenic Mice via Inhibition of Nuclear Factor-κB and NLRP3 Inflammasome Activation

Autor:	Xinxin Cheng, Jun Xu, Chu-Chu Zhang, Jian-Quan Shi, Ying-Dong Zhang, Xiu-Lan Sun, Jiang-Bo Wang, Hai-Qiang Zou
Rok vydání:	2013
Předmět:	Genetically modified mouse Inflammasomes Amyloid beta Transgene NALP3 Mice Transgenic Plaque Amyloid Pharmacology Amyloid beta-Protein Precursor Antimalarials Mice Alzheimer Disease In vivo Physiology (medical) NLR Family Pyrin Domain-Containing 3 Protein parasitic diseases Presenilin-1 medicine Animals Pharmacology (medical) Artemisinin Neuroinflammation Inflammation Neurons biology Chemistry NF-kappa B Inflammasome Original Articles Artemisinins Up-Regulation Psychiatry and Mental health biology.protein Carrier Proteins medicine.drug
Zdroj:	CNS Neuroscience & Therapeutics. 19:262-268
ISSN:	1755-5930
DOI:	10.1111/cns.12066
Popis:	Summary 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. Aims 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.
Databáze:	OpenAIRE
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