神经炎症
神经退行性变
细胞生物学
先天免疫系统
生物
小胶质细胞
促炎细胞因子
模式识别受体
受体
特里夫
信号转导
免疫系统
神经科学
炎症
Toll样受体
免疫学
医学
疾病
病理
生物化学
作者
Marı́a Pascual,María Calvo-Rodríguez,Lucı́a Núñez,Carlos Villalobos,Juán Ureña,Consuelo Guerri
出处
期刊:Iubmb Life
[Wiley]
日期:2021-06-04
卷期号:73 (7): 900-915
被引量:36
摘要
Toll-like receptors (TLRs) or pattern recognition receptors respond to pathogen-associated molecular patterns (PAMPs) or internal damage-associated molecular patterns (DAMPs). TLRs are integral membrane proteins with both extracellular leucine-rich and cytoplasmic domains that initiate downstream signaling through kinases by activating transcription factors like AP-1 and NF-κB, which lead to the release of various inflammatory cytokines and immune modulators. In the central nervous system, different TLRs are expressed mainly in microglia and astroglial cells, although some TLRs are also expressed in oligodendroglia and neurons. Activation of TLRs triggers signaling cascades by the host as a defense mechanism against invaders to repair damaged tissue. However, overactivation of TLRs disrupts the sustained immune homeostasis-induced production of pro-inflammatory molecules, such as cytokines, miRNAs, and inflammatory components of extracellular vesicles. These inflammatory mediators can, in turn, induce neuroinflammation, and neural tissue damage associated with many neurodegenerative diseases. This review discusses the critical role of TLRs response in Alzheimer's disease, Parkinson's disease, ischemic stroke, amyotrophic lateral sclerosis, and alcohol-induced brain damage and neurodegeneration.
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