NLRP3炎症小体在神经退行性疾病中的研究进展

Research progresses of NLRP3 inflammasome in neurodegenerative diseases

炎症小体是由模式识别受体(pattern recognition receptors, PRRs)、接头蛋白ASC(apoptosis-associated speck-like protein containing a CARD)以及效应分子半胱氨酸依赖性的天冬氨酸水解酶-1的前体(pro-caspase-1)三部分构成的结构复杂的多蛋白复合物,其中以NLRP3(NLRfamilypyrindomaincontaining 3)炎症小体研究最为广泛。NLRP3炎症小体作为先天免疫的重要组成部分,其介导的神经炎症对一些神经退行性疾病的发生发展具有关键作用,如阿尔茨海默症(Alzheimer’s disease, AD)、帕金森病(Parkinson’s disease, PD)、肌萎缩侧索硬化症(amyotrophic lateral sclerosis, ALS)、多发性硬化症(multiple sclerosis, MS)等都受NLRP3炎症小体的调控。本综述主要就NLRP3炎症小体的结构和功能、激活与调节机制以及NLRP3炎症小体在几种神经退行性疾病发生发展和治疗中的作用等方面进行阐述。

Inflammasome is a complicated polyprotein complexes, which consists of three parts: pattern recognition receptors(PRRs), apoptosis-associated speck-like protein containing a CARD(ASC) and precursor of cysteine-dependent aspartate hydrolase 1(pro-caspase-1). As an important part of innate immunity, NLRP3 inflammasome is the most widely studied inflammasome. Neuroinflammation mediated by NLRP3 inflammasome plays a key role in the development of some neurodegenerative diseases, such as Alzheimer’s disease(AD), Parkinson’s disease(PD), amyotrophic lateral sclerosis(ALS) and multiple sclerosis(MS). All the diseases above are regulated by NLRP3 inflammasome. This review focused on the structure and function of NLRP3 inflammasome, the activating and regulatory mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in the pathogenesis, progression and therapy of several neurodegenerative diseases.