Shen Yao, Qian Liyin, Luo Hu, Li Xiaofang, Ruan Yuer, Fan Runyue, Si Zizhen, Chen Yunpeng, Li Longhui, Liu Yu
Department of Public Health, School of Medicine, Ningbo University, Ningbo 315021, China.
Department of Psychology, Faculty of Teacher Education, Ningbo University, Ningbo 315021, China.
Brain Sci. 2022 Aug 10;12(8):1057. doi: 10.3390/brainsci12081057.
The NLRP inflammasome is a multi-protein complex which mainly consists of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain. Its activation is linked to microglial-mediated neuroinflammation and partial neuronal degeneration. Many neuropsychiatric illnesses have increased inflammatory responses as both a primary cause and a defining feature. The NLRP inflammasome inhibition delays the progression and alleviates the deteriorating effects of neuroinflammation on several neuropsychiatric disorders. Evidence on the central effects of the NLRP inflammasome potentially provides the scientific base of a promising drug target for the treatment of neuropsychiatric disorders. This review elucidates the classification, composition, and functions of the NLRP inflammasomes. It also explores the underlying mechanisms of NLRP inflammasome activation and its divergent role in neuropsychiatric disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, depression, drug use disorders, and anxiety. Furthermore, we explore the treatment potential of the NLRP inflammasome inhibitors against these disorders.
NLRP炎性小体是一种多蛋白复合物,主要由核苷酸结合寡聚化结构域、富含亮氨酸重复序列和pyrin结构域组成。其激活与小胶质细胞介导的神经炎症和部分神经元变性有关。许多神经精神疾病都有炎症反应增加的情况,这既是主要病因,也是一个决定性特征。NLRP炎性小体的抑制作用可延缓多种神经精神疾病的进展,并减轻神经炎症的恶化影响。关于NLRP炎性小体中枢作用的证据可能为治疗神经精神疾病提供一个有前景的药物靶点的科学依据。这篇综述阐述了NLRP炎性小体的分类、组成和功能。它还探讨了NLRP炎性小体激活的潜在机制及其在神经精神疾病中的不同作用,包括阿尔茨海默病、亨廷顿病、帕金森病、抑郁症、药物使用障碍和焦虑症。此外,我们还探讨了NLRP炎性小体抑制剂对这些疾病的治疗潜力。