Репозиторий Университета

© 2018 Meditsina Publishers. All rights reserved. NLR family of receptors are important members of the innate immunity that respond to exogenous pathogens and endogenous danger signals. Activation of NLR leads to formation of a multimolecular complex called an inflammasome. This complex is used to drive the processing and release of pro-inflammatory cytokines IL-1β and IL-18. Defects in regulation of an inflammasome activation underlie the development of a series of autoinflammatory diseases such as cryopyrin-associated periodic syndromes, familial Mediterranean fever and others. In this review we discuss forms of pathology associated with mutations and gene polymorphism of inflammasomes NLRP3, NLRP1, NLRС2 and NLRP12.

© 2018, Media Sphera Publishing Group. All rights reserved. Inflammasomes are macromolecular complexes that contain many copies of receptors recognizing molecular patterns of pathogenic agents (PAMP) and damage-associated structures (DAMP), and also include molecules of adapter protein ASC and procaspase- 1. Activation of inflammasomes leads to the formation of active caspase-1 that, in turn, provides the maturation of pro-IL-1β and pro-IL-18 to IL-1β and IL-18. The latter cytokines play an important role in control of neuroinlfammation in the central nervous system contributing to the pathogenesis of a series of neurological, neurodegenerative and mental disorders. The review discusses the involvement of NLRP3 inflammasome and other their types in the development of the traumatic brain injury, ischemic and hemorrhagic stroke, brain tumors, CNS infections, Alzheimer’s and Parkinson’s diseases, epilepsy, amyotrophic lateral sclerosis, depressiver, and consequences of alcohol abuse. The elucidation of molecular mechanisms and signaling pathways controlled by inflammasomes will allow the development of new therapeutic measures for diseases, in which neuroinflammation plays a leading pathogenetic role.

© 2018 Ima-Press Publishing House. All rights reserved. Human immuno-inflammatory diseases (IID), depending on the predominant mechanisms of immune activation, are divided into two main categories: autoimmune and autoinflammatory. It is assumed that hyperproduction of "proin-flammatory" and immunoregulatory cytokine-interleukin 1 (IL 1) largely determines the "intersection" between the mechanisms underlying autoimmunity and autoinflammation in many IID. This review discusses the role of IL1 in the pathogenesis of IID, primarily those associated with the activation of NLRP3-inflammasome, and therapeutic perspectives of IL1β inhibition with monoclonal antibodies to IL1β - canakinumab. The study of the IL1 role in the regulation of interactions between innate (TLR activation, inflammasome) and adaptive (Th1 - and Th17-types of immune response) immunity and the efficacy of IL1 inhibitors may be important in terms of decoding the patho-genetic mechanisms of IID and the development of new approaches to personalized therapy.