Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, PR China.
Department of Clinical Laboratory Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, PR China.
Biomed Pharmacother. 2021 Jun;138:111428. doi: 10.1016/j.biopha.2021.111428. Epub 2021 Mar 2.
In an ageing society, neurodegenerative diseases have attracted attention because of their high incidence worldwide. Despite extensive research, there is a lack of conclusive insights into the pathogenesis of neurodegenerative diseases, which limit the strategies for symptomatic treatment. Therefore, better elucidation of the molecular mechanisms involved in neurodegenerative diseases can provide an important theoretical basis for the discovery of new and effective prevention and treatment methods. The innate immune system is activated during the ageing process and in response to neurodegenerative diseases. Inflammasomes are multiprotein complexes that play an important role in the activation of the innate immune system. They mediate inflammatory reactions and pyroptosis, which are closely involved in neurodegeneration. There are different types of inflammasomes, although the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is the most common inflammasome; NLRP3 plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we will discuss the mechanisms that are involved in the activation of the NLRP3 inflammasome and its crucial role in the pathology of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. We will also review various treatments that target the NLRP3 inflammasome pathway and alleviate neuroinflammation. Finally, we will summarize the novel treatment strategies for neurodegenerative disorders.
在老龄化社会中，神经退行性疾病由于其在全球范围内的高发病率而受到关注。尽管进行了广泛的研究，但对神经退行性疾病的发病机制仍缺乏明确的认识，这限制了对症治疗的策略。因此，更好地阐明神经退行性疾病中涉及的分子机制，可以为发现新的、有效的预防和治疗方法提供重要的理论基础。在衰老过程中和应对神经退行性疾病时，固有免疫系统会被激活。炎性小体是多蛋白复合物，在固有免疫系统的激活中发挥重要作用。它们介导炎症反应和细胞焦亡，这与神经退行性变密切相关。存在不同类型的炎性小体，尽管核苷酸结合寡聚化结构域样受体热蛋白结构域包含蛋白 3（NLRP3）炎性小体是最常见的炎性小体；NLRP3 在神经退行性疾病的发病机制中发挥重要作用。在这篇综述中，我们将讨论激活 NLRP3 炎性小体的机制及其在神经退行性疾病（如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多发性硬化症）发病机制中的关键作用。我们还将回顾针对 NLRP3 炎性小体途径的各种治疗方法，并减轻神经炎症。最后，我们将总结神经退行性疾病的新治疗策略。
