Abstract—

Alcoholism is a global socially significant problem, which still remains one of the leading causes of disability and premature death. One of the main signs of the disease is the loss of cognitive control over the amount of alcohol consumed. Among the mechanisms of the development of this pathology, changes in neuroimmune mechanisms occurring in the brain during prolonged alcohol consumption and its withdrawal have recently become in the focus of numerous studies. Ethanol consumption leads to the activation of neuroimmune signaling in the central nervous system through many subtypes of Toll-like receptors (TLRs), as well as release of their endogenous agonists (HMGB1 protein, S100 protein, heat shock proteins, extracellular matrix degradation proteins). TLR activation triggers intracellular molecular cascades of reactions leading to increased expression of genes of the innate immune system, particularly, proinflammatory cytokines, causing further development of a persistent neuroinflammatory process in the central nervous system, which leads to death of neurons and neuroglial cells in various brain structures, primarily in those, which are associated with the development of a pathological craving for alcohol. In addition, there is evidence that some subtypes of TLRs (TLR3, TLR4) are able to form heterodimers with neuropeptide receptors, thereby possibly playing other roles in the central nervous system, in addition to participating in the activation of the innate immune system.

中文翻译：

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Toll样受体在酒精中毒神经免疫学中的作用

摘要—

酒精中毒是一个全球性的，具有社会意义的问题，仍然是残疾和过早死亡的主要原因之一。该疾病的主要症状之一是对所消耗的酒精量失去认知控制。在这种病理学发展的机制中，长期饮酒及其戒断期间大脑中发生的神经免疫机制的变化近来已成为众多研究的重点。乙醇的消耗通过Toll样受体（TLR）的许多亚型导致中枢神经系统中神经免疫信号的激活，以及释放它们的内源性激动剂（HMGB1蛋白，S100蛋白，热休克蛋白，细胞外基质降解蛋白） 。TLR激活触发细胞内分子级联反应，从而导致先天免疫系统（尤其是促炎性细胞因子）的基因表达增加，导致中枢神经系统中持续的神经炎性过程进一步发展，从而导致各种神经元和神经胶质细胞死亡大脑结构，主要是那些与酒精的病理渴望相关的结构。另外，有证据表明，TLR的某些亚型（TLR3，TLR4）能够与神经肽受体形成异二聚体，从而除了参与先天免疫系统的激活外，还可能在中枢神经系统中发挥其他作用。导致中枢神经系统中持续性神经炎性过程的进一步发展，这导致各种脑部结构（主要是那些与酒精的病理渴望有关）的神经元和神经胶质细胞死亡。此外，有证据表明，TLR的某些亚型（TLR3，TLR4）能够与神经肽受体形成异二聚体，从而除了参与先天免疫系统的激活外，还可能在中枢神经系统中发挥其他作用。导致中枢神经系统中持续性神经炎性过程的进一步发展，这导致各种脑部结构（主要是那些与酒精的病理渴望有关）的神经元和神经胶质细胞死亡。此外，有证据表明，TLR的某些亚型（TLR3，TLR4）能够与神经肽受体形成异二聚体，从而除了参与先天免疫系统的激活外，还可能在中枢神经系统中发挥其他作用。