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The Role of Toll-Like Receptors in Neuroimmunology of Alcoholism

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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.

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Authors and Affiliations

  1. Institute of Experimental Medicine, ul. Akad. Pavlova 12, 197376, St. Petersburg, Russia

    M. I. Airapetov, A. A. Lebedev, E. R. Bychkov & P. D. Shabanov

  2. St. Petersburg State Medical Pediatric University, ul. Litovskaya 2, 194100, St. Petersburg, Russia

    M. I. Airapetov

  3. University ITMO (National Research University), pr. Kronverkskyi 49, 197101, St. Petersburg, Russia

    S. O. Eresko

  4. Kirov Military Medical Academy, ul. Akad. Lebedeva 6, 194044, St. Petersburg, Russia

    P. D. Shabanov

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  1. M. I. Airapetov
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Airapetov, M.I., Eresko, S.O., Lebedev, A.A. et al. The Role of Toll-Like Receptors in Neuroimmunology of Alcoholism. Biochem. Moscow Suppl. Ser. B 15, 71–79 (2021). https://doi.org/10.1134/S1990750821010029

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