Alzheimer’s disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. The typical pathological characteristics of AD are extracellular senile plaques composed of amyloid ß (Aβ) protein, intracellular neurofibrillary tangles formed by the hyperphosphorylation of the microtubule-associated protein tau, and neuron loss. In the past hundred years, although human beings have invested a lot of manpower, material and financial resources, there is no widely recognized drug for the effective prevention and clinical cure of AD in the world so far. Therefore, evaluating and exploring new drug targets for AD treatment is an important topic. At present, researchers have not stopped exploring the pathogenesis of AD, and the views on the pathogenic factors of AD are constantly changing. Multiple evidence have confirmed that chronic neuroinflammation plays a crucial role in the pathogenesis of AD. In the field of neuroinflammation, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a key molecular link in the AD neuroinflammatory pathway. Under the stimulation of Aβ oligomers and tau aggregates, it can lead to the assembly and activation of NLRP3 inflammasome in microglia and astrocytes in the brain, thereby causing caspase-1 activation and the secretion of IL-1β and IL-18, which ultimately triggers the pathophysiological changes and cognitive decline of AD. In this review, we summarize current literatures on the activation of NLRP3 inflammasome and activation-related regulation mechanisms, and discuss its possible roles in the pathogenesis of AD. Moreover, focusing on the NLRP3 inflammasome and combining with the upstream and downstream signaling pathway-related molecules of NLRP3 inflammasome as targets, we review the pharmacologically related targets and various methods to alleviate neuroinflammation by regulating the activation of NLRP3 inflammasome, which provides new ideas for the treatment of AD.
The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.
ObjectiveTo explore the association between lipoprotein-related phospholipase A2 (Lp-PLA2) and the risk of Parkinson’s disease (PD).MethodsA case-control study involving 58 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected. According to the disease course and severity, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD patients was investigated using receiver’s operator characteristic curves.ResultsLp-PLA2 level was significantly higher in the PD patients compared with the controls, and was significantly and positively correlated with the Hoehn-Yahr (H&Y) stage. The serum Lp-PLA2 level and H&Y stage of PD patients with a longer disease course were significantly higher than those with a shorter disease course. PD patients with milder conditions had significantly lower serum Lp-PLA2 levels than patients with severe conditions. Multivariable logistic regression analysis indicated higher Lp-PLA2 level was an independent risk factor of PD patients. Moreover, the area under the curve for Lp-PLA2 was 0.703, which was between those of homocysteine and serum amylase A.ConclusionTo our knowledge, this is the first study to show that increased level of Lp-PLA2 is associated with the risk of PD. Lp-PLA2 may be used for early detection of PD, and provides an effective intervention target for clinical treatment of PD.
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