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

2020 ◽  
Vol 77 (3) ◽  
pp. 923-934
Author(s):  
Jian-Quan Shi ◽  
Bian-Rong Wang ◽  
Teng Jiang ◽  
Li Gao ◽  
Ying-Dong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Particulate Matter ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Fine Particulate Matter ◽  
Transport Pathway ◽  
Critical Gap ◽  
Fine Particulate ◽  
Pm2.5 Exposure

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.

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

2021 ◽  
Author(s):  
Jian-Quan Shi ◽  
Bian-Rong Wang ◽  
Teng Jiang ◽  
Li Gao ◽  
Ying-Dong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Particulate Matter ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Fine Particulate Matter ◽  
Transport Pathway ◽  
Critical Gap ◽  
Fine Particulate ◽  
Pm2.5 Exposure

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.

Fine particulate matter is a potential determinant of Alzheimer's disease: A systemic review and meta-analysis

2019 ◽  
Vol 177 ◽  
pp. 108638 ◽  
Author(s):  
Tsung-Lin Tsai ◽  
Yu-Ting Lin ◽  
Bing-Fang Hwang ◽  
Shoji F. Nakayama ◽  
Chon-Haw Tsai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Particulate Matter ◽  
Meta Analysis ◽  
Fine Particulate Matter ◽  
Systemic Review ◽  
Fine Particulate ◽  
Potential Determinant

scholarly journals Fine Particulate Matter and Markers of Alzheimer’s Disease Neuropathology at Autopsy in a Community-Based Cohort

2021 ◽  
Vol 79 (4) ◽  
pp. 1761-1773
Author(s):  
Rachel M. Shaffer ◽  
Ge Li ◽  
Sara D. Adar ◽  
C. Dirk Keene ◽  
Caitlin S. Latimer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Particulate Matter ◽  
Fine Particulate Matter ◽  
Braak Stage ◽  
Community Based ◽  
Spatiotemporal Model ◽  
Fine Particulate ◽  
Autopsy Specimens

Background: Evidence links fine particulate matter (PM2.5) to Alzheimer’s disease (AD), but no community-based prospective cohort studies in older adults have evaluated the association between long-term exposure to PM2.5 and markers of AD neuropathology at autopsy. Objective: Using a well-established autopsy cohort and new spatiotemporal predictions of air pollution, we evaluated associations of 10-year PM2.5 exposure prior to death with Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC score). Methods: We used autopsy specimens (N = 832) from the Adult Changes in Thought (ACT) study, with enrollment ongoing since 1994. We assigned long-term exposure at residential address based on two-week average concentrations from a newly developed spatiotemporal model. To account for potential selection bias, we conducted inverse probability weighting. Adjusting for covariates with tiered models, we performed ordinal regression for Braak and CERAD and logistic regression for dichotomized ABC score. Results: 10-year average (SD) PM2.5 from death across the autopsy cohort was 8.2 (1.9) μg/m3. Average age (SD) at death was 89 (7) years. Each 1μg/m3 increase in 10-year average PM2.5 prior to death was associated with a suggestive increase in the odds of worse neuropathology as indicated by CERAD score (OR: 1.35 (0.90, 1.90)) but a suggestive decreased odds of neuropathology as defined by the ABC score (OR: 0.79 (0.49, 1.19)). There was no association with Braak stage (OR: 0.99 (0.64, 1.47)). Conclusion: We report inconclusive associations between PM2.5 and AD neuropathology at autopsy among a cohort where 94% of individuals experienced 10-year exposures below the current EPA standard. Prior studies of AD risk factors and AD neuropathology are similarly inconclusive, suggesting alternative mechanistic pathways for disease or residual confounding.

P1-030: ENVIRONMENTAL DETERMINANTS OF NEUROANATOMIC RISK FOR ALZHEIMER'S DISEASE IN OLDER WOMEN: ROLE OF FINE PARTICULATE MATTER

2006 ◽  
Vol 14 (7S_Part_4) ◽  
pp. P278-P278
Author(s):  
Diana Younan ◽  
Xinhui Wang ◽  
Andrew J. Petkus ◽  
Ramon Casanova ◽  
Ryan Barnard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Particulate Matter ◽  
Older Women ◽  
Fine Particulate Matter ◽  
Environmental Determinants ◽  
Fine Particulate

scholarly journals The Combined Effects of Fine Particulate Matter and Temperature on Preterm Birth in Seoul, 2010–2016

2021 ◽  
Vol 18 (4) ◽  
pp. 1463
Author(s):  
Youngrin Kwag ◽  
Min-ho Kim ◽  
Shinhee Ye ◽  
Jongmin Oh ◽  
Gyeyoon Yim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Preterm Birth ◽  
Pregnant Women ◽  
Low Temperatures ◽  
Fine Particulate Matter ◽  
Temperature Data ◽  
Fine Particulate ◽  
The Mean ◽  
Pm2.5 Exposure ◽  
Pm2.5 Concentration

Background: Preterm birth contributes to the morbidity and mortality of newborns and infants. Recent studies have shown that maternal exposure to particulate matter and extreme temperatures results in immune dysfunction, which can induce preterm birth. This study aimed to evaluate the association between fine particulate matter (PM2.5) exposure, temperature, and preterm birth in Seoul, Republic of Korea. Methods: We used 2010–2016 birth data from Seoul, obtained from the Korea National Statistical Office Microdata. PM2.5 concentration data from Seoul were generated through the Community Multiscale Air Quality (CMAQ) model. Seoul temperature data were collected from the Korea Meteorological Administration (KMA). The exposure period of PM2.5 and temperature were divided into the first (TR1), second (TR2), and third (TR3) trimesters of pregnancy. The mean PM2.5 concentration was used in units of ×10 µg/m3 and the mean temperature was divided into four categories based on quartiles. Logistic regression analyses were performed to evaluate the association between PM2.5 exposure and preterm birth, as well as the combined effects of PM2.5 exposure and temperature on preterm birth. Result: In a model that includes three trimesters of PM2.5 and temperature data as exposures, which assumes an interaction between PM2.5 and temperature in each trimester, the risk of preterm birth was positively associated with TR1 PM2.5 exposure among pregnant women exposed to relatively low mean temperatures (<3.4 °C) during TR1 (OR 1.134, 95% CI 1.061–1.213, p < 0.001). Conclusions: When we assumed the interaction between PM2.5 exposure and temperature exposure, PM2.5 exposure during TR1 increased the risk of preterm birth among pregnant women exposed to low temperatures during TR1. Pregnant women should be aware of the risk associated with combined exposure to particulate matter and low temperatures during TR1 to prevent preterm birth.

scholarly journals In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

2018 ◽  
Vol 46 (1) ◽  
pp. 148-159 ◽  
Author(s):  
Zhengmeng Ye ◽  
Xi Lu ◽  
Yi Deng ◽  
Xinquan Wang ◽  
Shuo Zheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Particulate Matter ◽  
Sodium Excretion ◽  
Fine Particulate Matter ◽  
In Utero ◽  
D1 Receptor ◽  
In Utero Exposure ◽  
Fine Particulate ◽  
Pm2.5 Exposure ◽  
Renal Dopamine

Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2.5–induced hypertension in the offspring. Methods: Pregnant Sprague–Dawley rats were given an oropharyngeal drip of PM2.5 (1.0 mg/kg) at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D1R were determined by immunoblotting. The phosphorylation of D1R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM2.5-treated dams had increased blood pressure, impaired sodium excretion, and reduced D1R-mediated natriuresis and diuresis, accompanied by decreased renal D1R expression and GRK4 expression. The impaired renal D1R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS) induced by PM2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks in the offspring of PM2.5-treated dam normalized the decreased renal D1R expression and increased renal D1R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM2.5 increases ROS and GRK4 expression, impairs D1R-mediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D1R function may be a target for the prevention and treatment of the hypertension in offspring of mothers exposed to PM2.5 during pregnancy.

Ambient Fine Particulate Matter and Preterm Birth in California: Identification of Critical Exposure Windows

2019 ◽  
Vol 188 (9) ◽  
pp. 1608-1615 ◽  
Author(s):  
Paige Sheridan ◽  
Sindana Ilango ◽  
Tim A Bruckner ◽  
Qiong Wang ◽  
Rupa Basu ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Preterm Birth ◽  
Proportional Hazards ◽  
Fine Particulate Matter ◽  
Cox Proportional Hazards ◽  
Distributed Lag ◽  
Fine Particulate ◽  
Cox Proportional Hazards Models ◽  
Pm2.5 Exposure ◽  
Exposure Windows

Abstract Exposure to ambient fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5)) during pregnancy is associated with preterm birth (PTB), a leading cause of infant morbidity and mortality. Results from studies attempting to identify etiologically relevant exposure periods of vulnerability have been inconsistent, possibly because of failure to consider the time-to-event nature of the outcome and lagged exposure effects of PM2.5. In this study, we aimed to identify critical exposure windows for weekly PM2.5 exposure and PTB in California using California birth cohort data from 2005–2010. Associations were assessed using distributed-lag Cox proportional hazards models. We assessed effect-measure modification by race/ethnicity by calculating the weekly relative excess risk due to interaction. For a 10-μg/m3 increase in PM2.5 exposure over the entire period of gestation, PTB risk increased by 11% (hazard ratio = 1.11, 95% confidence interval: 1.09, 1.14). Gestational weeks 17–24 and 36 were associated with increased vulnerability to PM2.5 exposure. We find that non-Hispanic black mothers may be more susceptible to effects of PM2.5 exposure than non-Hispanic white mothers, particularly at the end of pregnancy. These findings extend our knowledge about the existence of specific exposure periods during pregnancy that have the greatest impact on preterm birth.

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