NLRP3 Inflammasome: A Potential Therapeutic Target in Fine Particulate Matter-Induced Neuroinflammation in Alzheimer’s Disease

Article type: Review Article

Authors: Shi, Jian-Quan^a | Wang, Bian-Rong^b | Jiang, Teng^a | Gao, Li^c | Zhang, Ying-Dong^{a; *} | Xu, Jun^{d; *}

Affiliations: [a] Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China | [b] Department of Neurology, Geriatric Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China | [c] Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China | [d] Department of Cognitive Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China

Correspondence: [*] Correspondence to: Ying-Dong Zhang, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No.68 Changle Road, Nanjing, Jiangsu Province, 210006, PR China. E-mail: zhangyingdongnjmu@163.com. and Jun Xu, Department of Cognitive Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 West Section of South 4th Ring Road, Beijing 100070, P.R. China. E-mail: neurojun1@163.com or neurojun@126.com.

Abstract: As one of the most harmful air pollutants, fine particulate matter (PM2.5) has been implicated as a risk factor for multiple diseases, which has generated widespread public concern. Accordingly, a growing literature links PM2.5 exposure with Alzheimer’s disease (AD). A critical gap in our understanding of the adverse effects of PM2.5 on AD is the mechanism triggered by PM2.5 that contributes to disease progression. Recent evidence has demonstrated that PM2.5 can activate NLRP3 inflammasome-mediated neuroinflammation. In this review, we highlight the novel evidence between PM2.5 exposure and AD incidence, which is collected and summarized from neuropathological, epidemiological, and neuroimaging studies to in-depth deciphering molecular mechanisms. First, neuropathological, epidemiological, and neuroimaging studies will be summarized. Then, the transport pathway for central nervous system delivery of PM2.5 will be presented. Finally, the role of NLRP3 inflammasome-mediated neuroinflammation in PM2.5 induced-effects on AD will be recapitulated.

Keywords: Alzheimer’s disease, fine particulate matter, microglia, neuroinflammation, NLRP3 inflammasome

DOI: 10.3233/JAD-200359

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 923-934, 2020