NLRP1炎性小体的激活机制

Activation Mechanism of NLRP1 Inflammasome

核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)是NOD样受体(nucleotide-binding oligomerization domain-like receptors,NLRs)家族的成员,是人们发现的第一个能形成炎性小体的蛋白。NLRP1的激活可引起半胱氨酸蛋白酶-1前体(pro-caspase-1)的活化并进一步促进炎性因子的成熟和释放,在天然免疫中发挥着重要作用。NLRP1的结构在不同种属间存在差异,目前能引起NLRP1激活的机制,主要包括通过蛋白酶体途径降解并激活NLRP1、通过抑制DPP9激活NLRP1以及弓形虫和部分代谢抑制剂激活NLRP1等。某些病毒蛋白或RNA也能够激活NLRP1,其具体激活机制以及NLRP1在抗病毒感染中发挥的作用尚未明确,还有待于进一步研究。

Nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1) is a member of the NOD-like receptors(NLRs) family, and is the first NLR family protein found to form inflammasome. The activation of NLRP1 can cause the activation of pro-caspase-1 and further promote the maturation and release of inflammatory factors, which plays an important role in innate immunity. The domain structure of NLRP1 varies among different species. At present, the mechanisms that can cause NLRP1 activation mainly include degradation and activation of NLRP1 through proteasome pathway, activation of NLRP1 through inhibition of DPP9, and activation of NLRP1 by Toxoplasma gondii and some metabolic inhibitors. Some viral proteins or RNAs can also activate NLRP1. How the virus activates NLRP1 and the role of NLRP1 in antiviral infection are not clear, and need to be further studied.