Abstract Details

Title Anti-Malarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/PS1dE9 Transgenic Mice Via Inhibition of NF-?B and NLRP3 Inflammasome Activation

Topic Aging and Dementia

Presentation(s) IN9 - (-)

Poster/Presentation
Number 004

Objective

Background Neuroinflammation is thought to be the key mechanism linked to Alzheimer's disease (AD) pathogenesis, which is deeply invovled in amyloid plaques, neurofibrillary tangles and microglia activation. Artemisinin has been reported to exert anti-inflammatory effects but the exact machanism need to clarified, and the effect of downregulation of amyloid deposition indicates the new direction for AD secondary prevention strategies.

Design/Methods 5-month-old APPswe/PS1dE9 transgenic mice were used to evaluate the effects of artemisinin on AD pathogenesis, Five mice were injected with 40 mg/kg artemisinin in DMSO at the same time once daily, for continuous 30 days. The other five mice were injected with DMSO as control. Immunohistochemical staining, Western Blotting, ELISA were combined to evaluate the expression or levels of soluble and insoluble A?42, IL-6, TNF-?, IL-1?,LRP1, RAGE, APP carboxyl terminal, BACE1, PS1, Aph-1a, serine 536 phosphorylated NF-?B p65, NF-?B p65, I?B-?, serine 32 phosphorylated I?B-?, NALP3, Cleaved Caspase-1 (Asp297).

Results We found that artemisinin treatment can (1) decreased neuritic plaque burden; (2) didn't alter A? transport across the blood-brain barrier; (3) regulated APP processing via inhibiting ?-secretase activity; (4) inhibited NF-?B activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice. The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathlogy due to its effects on suppressing NF-?B activity and NALP3 inflammasome activation.

Conclusions The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathlogy due to its effects on suppressing NF-?B activity and NALP3 inflammasome activation. Furthermore, Our study suggests that artemisinin could be potent candidate in the secondary prevention drugs for AD.

Authors/Disclosures
PRESENTER	No disclosure on file
Jun Xu, MD (Beijing Tian Tan Hospital)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Andrea Formella, PharmD, BCPP (Supernus Pharmaceuticals)	Dr. Formella has received personal compensation for serving as an employee of Supernus Pharmaceuticals, Inc. Dr. Formella has stock in Supernus Pharmaceuticals, Inc..

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