Particulate matter aggravates Alzheimer's disease by activating the NLRP3 inflammasome to release ASC specks,Environmental Science: Nano

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Particulate matter aggravates Alzheimer's disease by activating the NLRP3 inflammasome to release ASC specks
Environmental Science: Nano ( IF 5.8 ) Pub Date : 2021-06-23 , DOI: 10.1039/d1en00361e
Runxiao Zheng _{1,

2,

3,

4,

5} , Jing Zhang _{5,

6,

7,

8} , Xiaoqing Han _{1,

2,

3,

4,

5} , Yunyun Wu _{5,

9,

10,

11} , Jiao Yan _{1,

2,

3,

4,

5} , Panpan Song _{1,

2,

3,

4,

5} , Yanjing Wang _{1,

2,

3,

4,

5} , Xiaqing Wu _{1,

2,

3,

4,

5} , Haiyuan Zhang _{1,

2,

3,

4,

5}

Affiliation

Growing evidence has revealed the potential risk of ambient particulate matter (PM) causing chronic toxic influence on the nervous system of humans; however, it remains unclear whether PM could exacerbate Alzheimer's disease (AD). PM_2.5 possesses complex physicochemical properties and can trigger various chronic toxicological responses, which potentially correlate with the aggravation of AD pathogenesis. Herein, PM_2.5 was found to be able to activate the NLRP3 inflammasome in microglial cells (BV2) through multiple approaches, leading to the release of ASC specks, which could accelerate Aβ aggregation and promote neuronal apoptosis. After intranasal exposure to PM_2.5 for 13 weeks, the hippocampus region of APP/PS1 mice showed the ASC speck release and Aβ aggregation. In addition, the high concentration of PM_2.5 could cause a marked neuronal hypocellularity and spatial memory ability deficits in APP/PS1 mice. These results suggest the intense correlation between PM_2.5 and AD based on the activation of the NLRP3 inflammasome.

中文翻译：

颗粒物质通过激活 NLRP3 炎症小体释放 ASC 斑点加重阿尔茨海默病

越来越多的证据揭示了环境颗粒物 (PM) 对人类神经系统造成慢性毒性影响的潜在风险；然而，目前尚不清楚 PM 是否会加剧阿尔茨海默病 (AD)。PM _2.5具有复杂的理化特性，可以引发各种慢性毒理学反应，这可能与 AD 发病机制的恶化有关。在此，发现PM _2.5能够通过多种途径激活小胶质细胞 (BV2) 中的 NLRP3 炎症小体，导致 ASC 斑点的释放，从而加速 Aβ 聚集并促进神经元凋亡。鼻内暴露于 PM _{2.5 后}13 周后，APP/PS1 小鼠海马区出现 ASC 斑点释放和 Aβ 聚集。此外，高浓度的 PM _2.5会导致 APP/PS1 小鼠出现明显的神经元细胞不足和空间记忆能力缺陷。这些结果表明，基于 NLRP3 炎症小体的激活，PM _2.5与 AD之间存在强烈的相关性。

更新日期：2021-07-14

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