Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

Author:

Chen Da-bao1,Gao Hua-wu1,Peng Cheng1,Pei Shao-qiang1,Dai An-ran1,Yu Xue-ting1,Zhou Peng123ORCID,Wang Yan123,Cai Biao123

Affiliation:

1. School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China

2. Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China

3. Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China

Abstract

Abstract Objectives Alzheimer’s disease (AD) is a hidden neurological degenerative disease, which main clinical manifestations are cognitive dysfunction, memory impairment and mental disorders. Neuroinflammation is considered as a basic response of the central nervous system. NLRP3 (Nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3) inflammasome is closely related to the occurrence of neuroinflammation. Activation of the NLRP3 inflammasome results in the release of cytokines, pore formation and ultimately pyroptosis, which has demonstrated one of the critical roles in AD pathogenesis. Inhibition of the activity of NLRP3 is one of the focuses of the research. Therefore, NLRP3 represents an attractive pharmacological target, and discovery compounds with good NLRP3 inhibitory activity are particularly important. Key findings Quinones have good neuroprotective effects and prevent AD, which may be related to their regulation of inflammatory response. The molecular docking was used to explore 12 quinones with AD prevention and treatment and NLRP3. Docking results showed that the combination of anthraquinones and NLRP3 were the best, and the top two chemical compounds were Purpurin and Rhein, which are the most promising NLRP3 inhibitors. Summary These quinones may provide the theoretical basis for finding lead compounds for novel neuroprotective agents.

Funder

National Natural Science Foundation of China

Distinguished Young Scholars Project of Natural Science Foundation of Anhui Province in China

Key Project Foundation of Natural Science Research in Universities of Anhui Province in China

Key Project Foundation of Natural Science Research of Anhui University of Chinese Medicine

Project Foundation of Support Program for the Excellent Young Faculties in Universities of Anhui Province in China

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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