Yu Juan, Zhao Zhanghong, Li Yuanyuan, Chen Jian, Huang Nanqu, Luo Yong
Department of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 563000, China.
National Drug Clinical Trial Institution, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China.
Heliyon. 2024 Mar 28;10(7):e28838. doi: 10.1016/j.heliyon.2024.e28838. eCollection 2024 Apr 15.
Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms like bradykinesia, tremors, and balance issues. The pathology is recognized by progressively degenerative nigrostriatal dopaminergic neurons (DANs) loss. Its exact pathogenesis is unclear. Numerous studies have shown that nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) contributes to the pathogenesis of PD. Previous studies have demonstrated that the over-activation of NLRP3 inflammasome in microglia indirectly leads to the loss of DANs, which can worsen PD. In recent years, autopsy analyses of PD patients and studies in PD models have revealed upregulation of NLRP3 expression within DANs and demonstrated that activation of NLRP3 inflammasome in neurons is sufficient to drive neuronal loss, whereas microglial activation occurs after neuronal death, and that inhibition of intraneuronal NLRP3 inflammasome prevents degeneration of DANs. In this review, we provide research evidence related to NLRP3 inflammasome in DANs in PD as well as focus on possible mechanisms of NLRP3 inflammasome activation in neurons, aiming to provide a new way of thinking about the pathogenesis and prevention of PD.
帕金森病(PD)是一种神经退行性疾病,具有运动症状,如运动迟缓、震颤和平衡问题。其病理特征为黑质纹状体多巴胺能神经元(DANs)逐渐退化性丧失。其确切发病机制尚不清楚。大量研究表明,核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)与PD的发病机制有关。先前的研究表明,小胶质细胞中NLRP3炎性小体的过度激活间接导致DANs丧失,从而使PD病情恶化。近年来,对PD患者的尸检分析以及在PD模型中的研究表明,DANs内NLRP3表达上调,并证明神经元中NLRP3炎性小体的激活足以导致神经元丧失,而小胶质细胞激活发生在神经元死亡之后,并且抑制神经元内NLRP3炎性小体可防止DANs退化。在本综述中,我们提供了与PD中DANs内NLRP3炎性小体相关的研究证据,并着重探讨了神经元中NLRP3炎性小体激活的可能机制,旨在为PD的发病机制和预防提供新的思路。