NLRP3 İnflamazom Aktivasyon ve Düzenleme Mekanizmalarına Genel Bir Bakış

Doğal bağışıklık sistemi, vücuda giren patojenlere karşı konakçı savunmasında hayati önem taşır. Doğal bağışıklık sisteminin bir bileşeni olan NLRP3 (NACHT-, LRR- ve pirin alanı içeren 3) inflamazom, multimerik bir protein kompleksidir. İnflamazom aktivasyonu klasik enflamatuvar cevaplardan farklı olarak başlayan ve gelişen bir süreçtir. NLRP3 inflamazom aktivasyonunun oluşması için DAMP'ler (Hasarlanma ile ilişkili moleküler modeller) ve PAMP'ler (Patojenle ilişkili moleküler modeller) gibi çeşitli tehlike sinyallerinin olması gerekir. Bu uyaranlara yanıt olarak, kaspaz-1 aktive olur. Aktif kaspaz-1 de, IL-1β (interlökin-1β) ve IL-18 (interlökin-18) sitokinlerinin öncül halde bulunan formlarını proteolitik olarak böler ve aktif hale getirir. Böylece IL-1β ve IL-18 aracılı enflamatuvar yanıtlar aktive olur. NLPR3 aktivasyonu önemli bir bağışıklık cevabı olmasına rağmen aşırı aktivasyonu enflamatuvar hastalıklara ve hücre ölümüne neden olabilmektedir. Bu nedenden dolayı, NLRP3 inflamazomunun regülasyonu ve inhibisyonu otoenflamatuvar hastalıklar için umut verici bir tedavi yaklaşımı olabilir. Bu derlemede, NLRP3 inflamazom aktivasyon mekanizmaları hakkındaki mevcut anlayışın yanı sıra standart olmayan ve alternatif inflamazom yolaklarındaki son gelişmeler sunulmuştur.

An Overview of NLRP3 Inflammasome Activation and Regulation Mechanisms

The innate immune system is vital in host defense against pathogens entering the body. The NLRP3 (NACHT-, LRR- and Pyrin Domain Containing 3) inflammasome, a component of the innate immune system, is a multimeric protein complex. Inflammasome activation is a process that starts and improves differently from classical inflammatory responses. In order to induce inflammasome activation, there must be a danger signal such as DAMP (Damage-Associated Molecular Pattern) or PAMP (Pathogen-Associated Molecular Pattern) detected. In response to these stimuli, caspase-1 is activated. This in turn leads to cleavage and maturation of potent pro-inflammatory cytokines, IL-1β (interleukin-1β) and IL-18 (interleukin-18) by mature caspase-1. Thus, inflammatory responses mediated by IL-1β and IL-18 are activated. Although NLPR3 activation is an important immune response, its overactivation can cause inflammatory disorders and cell death. For this reason, regulation and inhibition of the NLRP3 inflammasome may be a promising treatment approach for these autoinflammatory diseases. In this review presents the current understanding of the mechanisms of NLRP3 inflammasome activation, as well as recent advances in the non-canonical and alternative inflammasome pathways.

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