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.

中文翻译：

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神经炎症、神经变性和酒精引起的脑损伤中的 Toll 样受体

Toll 样受体 (TLR) 或模式识别受体响应病原体相关分子模式 (PAMP) 或内部损伤相关分子模式 (DAMP)。TLR 是完整的膜蛋白，具有富含亮氨酸的细胞外结构域和细胞质结构域，可通过激活 AP-1 和 NF-κB 等转录因子通过激酶启动下游信号传导，从而导致各种炎性细胞因子和免疫调节剂的释放。在中枢神经系统中，不同的 TLR 主要在小胶质细胞和星形胶质细胞中表达，尽管一些 TLR 也在少突胶质细胞和神经元中表达。TLR 的激活触发宿主的信号级联反应，作为抵御入侵者的防御机制，以修复受损组织。然而，TLR 的过度激活会破坏持续的免疫稳态诱导的促炎分子的产生，例如细胞因子、miRNA 和细胞外囊泡的炎症成分。反过来，这些炎症介质可以诱导与许多神经退行性疾病相关的神经炎症和神经组织损伤。这篇综述讨论了 TLR 反应在阿尔茨海默病、帕金森病、缺血性中风、肌萎缩性侧索硬化以及酒精引起的脑损伤和神经退行性变中的关键作用。