Abstract
The nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3 (NLRP3) is an important pattern recognition receptor in human innate immunity. Activation of the NLRP3 inflammasome play a key role in the pathogenesis of Alzheimer’s disease (AD). Theories explaining activation of the NLRP3 inflammasome include the reactive oxygen species theory, the lysosomal damage theory and the mitochondrial DNA theory. The NLRP3 activation promotes occurrence of AD by producing IL-1β, IL-18 and other cytokines, and then by affecting the deposition of Aβ and tau proteins. Over-activated NLRP3 inflammasome often impair cell function and induces immune-related diseases. Some mechanisms have been found to negatively regulate activation of the NLRP3 inflammasome, which may be through receptor binding blocking mechanism, autophagy related mechanism, abnormal cytokine secretion mechanism, or interference related gene expression regulation mechanism. In this review, we summarize the possible mechanisms by which the activation of NLRP3 inflammasomes affects the pathogenesis of AD, and the recent advances in the prevention and treatment of AD by controlling the activation of NLRP3 inflammasomes. By researching the activation or inactivation of NLRP3 inflammasome, it is possible to reveal the pathogenesis of AD from a new perspective and provide a new idea for the prevention and treatment of AD.
Highlights
With the increase in the elderly population, the incidence of Alzheimer’s disease (AD) has a trend of increasing year by year [1]
Chronic inflammation during AD is mainly mediated by abnormal immune function of brain cells, which is generally believed to be caused by the abnormal accumulation of some proteins in microglia, mainly related to the activation of NLRP3 inflammasomes [72]
As for the pathogenesis of AD, there have been the theory of b-amyloid protein, the theory of abnormal neurotransmitters, the theory of abnormal Tau protein metabolism and the theory of nerve cell apoptosis
Summary
Citation: Bai H and Zhang Q (2021) Activation of NLRP3 Inflammasome and Onset of Alzheimer’s Disease. The nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3 (NLRP3) is an important pattern recognition receptor in human innate immunity. Activation of the NLRP3 inflammasome play a key role in the pathogenesis of Alzheimer’s disease (AD). Theories explaining activation of the NLRP3 inflammasome include the reactive oxygen species theory, the lysosomal damage theory and the mitochondrial DNA theory. The NLRP3 activation promotes occurrence of AD by producing IL-1b, IL-18 and other cytokines, and then by affecting the deposition of Ab and tau proteins. Overactivated NLRP3 inflammasome often impair cell function and induces immune-related diseases. Some mechanisms have been found to negatively regulate activation of the NLRP3 inflammasome, which may be through receptor binding blocking mechanism, autophagy related mechanism, abnormal cytokine secretion mechanism, or interference related gene expression regulation mechanism. In this review, we summarize the possible mechanisms by which the activation of NLRP3 inflammasomes affects the pathogenesis of AD, and the recent advances in the prevention and treatment of AD by controlling the activation of NLRP3 inflammasomes. By researching the activation or inactivation of NLRP3 inflammasome, it is possible to reveal the pathogenesis of AD from a new perspective and provide a new idea for the prevention and treatment of AD. Keywords: Alzheimer’s disease, inflammasome, pathogenesis, activation, nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3 Abbreviations: Ab, b-amyloid protein; ABRO1, Abraxas Brother 1; AD, Alzheimer’s disease; APP, Amyloid precursor protein; ASC, Apoptosis associated speck like protein containing cysteine aspartic proteinase recruitment domain; ATP, Adenosine triphosphate; BRCC3, Breast cancer susceptibility gene complex subunit protein 3; CARD, Cysteine aspartic proteinase recruitment domain; CD36, Cluster Of Differentiation 36; EPM, Endogenous pathogenic molecules; GMF, Glial mature factor; D4T, 2′,3′-Didehydro-3′-deoxythymidine (Stavudine); DAMP, danger associated molecule patterns; IL-18, Interleukin 18; LPS, Lipopolysaccharide; LTP, Long term potentiation; MG132, Carbobenzoxy-Leu-Leu-leucinal; mtDNA, Mitochondrial deoxyribonucleic acid; NEK 7, never in mitosis gene A related Kinase 7; NF-kB, Nuclear transcription factor kappa B; NLR, Nucleotide-conjugated oligomeric domain-like receptor; NLRC4, Nucleotide-conjugated oligomeric domain-like receptor family cysteine aspartic proteinase recruitment domain domain-containing 4; NLRP3:Nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3; NOD, Nucleotide-conjugated oligomeric domain; P2X7R, Purinergic ligand-gated ion channel 7 receptor; PAMP, Pathogen-associated molecular pattern; PG, Progesterone; pro-IL-1b, Interleukin1 beta precursor protein; PS1, Presenilin-1; PYD, pyrimidine nucleoside; ROS, Reactive oxygen species; RS, Radix Scrophulariae; STAT, Signal transduction and transcriptional activation factor; TRX, Thioredoxin; TXNIP, Thioredoxin interaction protein.
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