NLRP3 Inflammasome: An Emerging Therapeutic Target for Alzheimer’s Disease

Article type: Review Article

Authors: Tao, Shuqi^{a; 1} | Fan, Wenyuan^{a; 1} | Liu, Jinmeng^{b; 1} | Wang, Tong^c | Zheng, Haoning^a | Qi, Gaoxiu^d | Chen, Yanchun^{b; e} | Zhang, Haoyun^b | Guo, Zhangyu^{a; b; *} | Zhou, Fenghua^{a; b; *}

Affiliations: [a] Department of Pathology, School of Basic Medical Sciences, Weifang Medical University, Weifang, Shandong Province, China | [b] Neurologic Disorders and Regenerative Repair Laboratory, Weifang Medical University, Weifang, Shandong Province, China | [c] Department of Neurosurgery, Wei Fang People’s Hospital, Weifang, Shandong Province, China | [d] Department of Pathology, Affiliated Hospital, Weifang Medical University, Weifang, Shandong Province, China | [e] Department of Histology and Embryology, School of Basic Medical Sciences, Weifang Medical University, Weifang, Shandong Province, China

Correspondence: [*] Correspondence to: Zhangyu Guo and Fenghua Zhou, Department of Pathology, Weifang Medical University, Weifang 261053, Shandong Province, China. E-mails: [email protected], [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is currently the most prevalent neurological disease, and no effective and practical treatments and therapies exist. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3) inflammasome is vital in the human innate immune response. However, when the NLRP3 inflammasome is overactivated by persistent stimulation, several immune-related diseases, including AD, atherosclerosis, and obesity, result. This review will focus on the composition and activation mechanism of the NLRP3 inflammasome, the relevant mechanisms of involvement in the inflammatory response to AD, and AD treatment targeting NLRP3 inflammasome. This review aims to reveal the pathophysiological mechanism of AD from a new perspective and provide the possibility of more effective and novel strategies for preventing and treating AD.

Keywords: Alzheimer’s disease, amyloid-β, inhibitors, NLRP3 inflammasome, tau, treatment

DOI: 10.3233/JAD-230567

Journal: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1383-1398, 2023