Zeng Nannan, Wang Qi, Zhang Chong, Zhou Yali, Yan Jianguo
Department of Physiology, Guilin Medical University, Guilin, 541004, China; Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, 541004, China.
Department of Neurology, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541100, China.
Neurochem Int. 2023 Nov;170:105610. doi: 10.1016/j.neuint.2023.105610. Epub 2023 Sep 11.
Parkinson's disease (PD) is a neurodegenerative disease for which the prevalence is second only to Alzheimer's disease (AD). This disease primarily affects people of middle and old age, significantly impacting their health and quality of life. The main pathological features include the degenerative nigrostriatal dopaminergic (DA) neuron loss and Lewy body (LB) formation. Currently, available PD medications primarily aim to alleviate clinical symptoms, however, there is no universally recognized therapy worldwide that effectively prevents, clinically treats, stops, or reverses the disease. Consequently, the evaluation and exploration of potential therapeutic targets for PD are of utmost importance. Nevertheless, the pathophysiology of PD remains unknown, and neuroinflammation mediated by inflammatory cytokines that prompts neuron death is fundamental for the progression of PD. The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a key complex of proteins linking the neuroinflammatory cascade in PD. Moreover, mounting evidence suggests that traditional Chinese medicine (TCM) alleviates PD by suppressing the NLRP3 inflammasome. This article aims to comprehensively review the available studies on the composition and activating mechanism of the NLRP3 inflammasome, along with its significance in PD pathogenesis and potential treatment targets. We also review natural products or synthetic compounds which reduce neuroinflammation via modulating NLRP3 inflammasome activity, aiming to identify new targets for future PD diagnosis and treatment through the exploration of NLRP3 inhibitors. Additionally, this review offers valuable references for developing new PD treatment methods.
帕金森病(PD)是一种神经退行性疾病,其患病率仅次于阿尔茨海默病(AD)。这种疾病主要影响中老年人,对他们的健康和生活质量产生重大影响。主要病理特征包括黑质纹状体多巴胺能(DA)神经元变性丢失和路易小体(LB)形成。目前,现有的帕金森病药物主要旨在缓解临床症状,然而,全球尚无普遍认可的能有效预防、临床治疗、阻止或逆转该疾病的疗法。因此,评估和探索帕金森病的潜在治疗靶点至关重要。尽管如此,帕金森病的病理生理学仍不清楚,由炎性细胞因子介导的神经炎症促使神经元死亡是帕金森病进展的关键因素。含核苷酸结合寡聚化结构域样受体吡咯结构域3(NLRP3)炎性小体是连接帕金森病神经炎症级联反应的关键蛋白复合体。此外,越来越多的证据表明,中药通过抑制NLRP3炎性小体来缓解帕金森病。本文旨在全面综述关于NLRP3炎性小体的组成、激活机制及其在帕金森病发病机制中的意义和潜在治疗靶点的现有研究。我们还综述了通过调节NLRP3炎性小体活性来减轻神经炎症的天然产物或合成化合物,旨在通过探索NLRP3抑制剂来确定未来帕金森病诊断和治疗的新靶点。此外,本综述为开发新的帕金森病治疗方法提供了有价值的参考。