Affiliations: [a] Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| [b] Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| [c] Department of Pharmacy, The People’s Hospital of Gaozhou, Maoming, China
Correspondence:
[*]
Correspondence to: Yan Wang, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. E-mail: [email protected].
Note: [1] Yunfeng Li and Xiongjin Chen contributed equally to this paper.
Abstract: Alzheimer’s disease is a pervasive neurodegenerative disease that is estimated to represent approximately 70% of dementia cases worldwide, and the molecular complexity that has been highlighted remains poorly understood. The accumulation of extracellular amyloid-β (Aβ), intracellular neurofibrillary tangles formed by tau hyperphosphorylation, and neuroinflammation are the major pathological features of Alzheimer’s disease (AD). Over the years, there has been no apparent breakthrough in drug discovery based on the Aβ and tau hypotheses. Neuroinflammation has gradually become a hot spot in AD treatment research. As the primary cells of innate immunity in the central nervous system, microglia play a key role in neuroinflammation. Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes are vital molecules in neuroinflammation. In the pathological context of AD, the complex interplay between TLR4 and the NLRP3 inflammasomes in microglia influences AD pathology via neuroinflammation. In this review, the effect of the activation and inhibition of TLR4 and NLRP3 in microglia on AD pathology, as well as the cross-talk between TLR4 and the NLRP3 inflammasome, and the influence of essential molecules in the relevant signaling pathway on AD pathology, were expounded. In addition, the feasibility of these factors in representing a potential treatment option for AD has been clarified.
