TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease

小胶质细胞 神经炎症 炎症体 先天免疫系统 神经退行性变 神经科学 生物 突触修剪 炎症 免疫系统 补体系统 细胞生物学 免疫学 医学 病理 疾病
作者
Junling Yang,Leslie Wise,Ken‐ichiro Fukuchi
出处
期刊:Frontiers in Immunology [Frontiers Media SA]
卷期号:11 被引量:256
标识
DOI:10.3389/fimmu.2020.00724
摘要

Amyloid plaques, mainly composed of abnormally aggregated amyloid β-protein (Aβ) in the brain parenchyma, and neurofibrillary tangles (NFTs), composed of abnormal aggregates of hyperphosphorylated tau protein in neurons, are two pathological hallmarks of Alzheimer’s disease (AD). Fibrillar Aβ deposits and tau aggregates in the brain are accompanied with neuroinflammation and synapse loss, characterized by activated microglia and dystrophic neurites. Genome-wide association studies on patients with late-onset AD have identified a dozen genetic risk variants that are involved in innate immune responses, highlighting the importance of immune cells in the pathogenesis of late-onset AD. Additional lines of evidence support the notion that activated microglia, innate immune cells in the central nervous system (CNS), play pivotal, dual roles in AD progression: either clearing Aβ deposits by phagocytosis and promoting neuron survival and plasticity or releasing cytotoxic chemicals, inflammatory cytokines, exacerbating Aβ load and synaptotoxicity. Aggregated Aβ binds to toll-like receptor 4 (TLR4) and activates microglia, resulting in increased phagocytosis and cytokine production. Complement components are associated with amyloid plaques and NFTs. Aggregated Aβ can activate complement, leading to synapse pruning and loss by microglial phagocytosis. Systemic inflammation can activate microglial TLR4, NLRP3 inflammasome, and complement in the brain, leading to neuroinflammation, Aβ accumulation, synapse loss and neurodegeneration. The host immune response has been shown to function through complex crosstalk between the TLR, complement and inflammasome signaling pathways. Accordingly, targeting the molecular mechanisms underlying the TLR-complement-NLRP3 inflammasome signaling pathways can be a preventive and therapeutic approach for AD.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
潜山耕之完成签到,获得积分10
1秒前
1秒前
HQQ发布了新的文献求助10
1秒前
1秒前
1秒前
月影发布了新的文献求助10
1秒前
3秒前
条鱼完成签到,获得积分10
3秒前
nakl完成签到,获得积分10
3秒前
冷静发布了新的文献求助10
3秒前
3秒前
Joseph_LIN完成签到,获得积分10
3秒前
4秒前
4秒前
4秒前
田様应助prisfanstein采纳,获得10
4秒前
科目三应助zchen03采纳,获得10
4秒前
xx7508完成签到,获得积分10
4秒前
5秒前
5秒前
bonnwangyong完成签到,获得积分10
5秒前
Lucas应助勤劳半青采纳,获得20
6秒前
学术智子完成签到,获得积分10
6秒前
知性的绮兰完成签到,获得积分10
6秒前
6秒前
英姑应助lili采纳,获得10
6秒前
一口吃三个月亮完成签到,获得积分10
7秒前
大模型应助oo采纳,获得10
7秒前
kma完成签到,获得积分10
8秒前
大力哈密瓜完成签到,获得积分20
8秒前
Jasper应助学习中采纳,获得10
8秒前
8秒前
PGTrump完成签到,获得积分10
8秒前
小杜完成签到,获得积分20
9秒前
起起完成签到,获得积分10
9秒前
Lucien举报瓜小求助涉嫌违规
9秒前
村上春树不上树完成签到,获得积分10
9秒前
jelly发布了新的文献求助10
9秒前
闪闪鬼神发布了新的文献求助30
9秒前
Qing完成签到,获得积分10
9秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
England and the Discovery of America, 1481-1620 600
電気学会論文誌D(産業応用部門誌), 141 巻, 11 号 510
Exploring the effects of an evidenced-based professional development programme on teaching and learning in Chinese kindergartens 500
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3575717
求助须知:如何正确求助?哪些是违规求助? 3145750
关于积分的说明 9462234
捐赠科研通 2847209
什么是DOI,文献DOI怎么找? 1565025
邀请新用户注册赠送积分活动 732773
科研通“疑难数据库(出版商)”最低求助积分说明 719324