Department of Applied Life Science & Integrated Bioscience, Graduate School, Konkuk University, Chungju-si, South Korea.
Department of Integrated Bioscience & Biotechnology, Research Institute of Inflammatory Disease (RID), College of Biomedical and Health Science, Konkuk University, Chungju-si, South Korea.
Front Immunol. 2019 May 10;10:1000. doi: 10.3389/fimmu.2019.01000. eCollection 2019.
Neuronal dysfunction initiates several intracellular signaling cascades to release different proinflammatory cytokines and chemokines, as well as various reactive oxygen species. In addition to neurons, microglia, and astrocytes are also affected by this signaling cascade. This release can either be helpful, neutral or detrimental for cell survival. Toll-like receptors (TLRs) activate and signal their downstream pathway to activate NF-κB and pro-IL-1β, both of which are responsible for neuroinflammation and linked to the pathogenesis of different age-related neurological conditions. However, herein, recent aspects of polyphenols in the treatment of neurodegenerative diseases are assessed, with a focus on TLR regulation by polyphenols. Different polyphenol classes, including flavonoids, phenolic acids, phenolic alcohols, stilbenes, and lignans can potentially target TLR signaling in a distinct pathway. Further, some polyphenols can suppress overexpression of inflammatory mediators through TLR4/NF-κB/STAT signaling intervention, while others can reduce neuronal apoptosis via modulating the TLR4/MyD88/NF-κB-pathway in microglia/macrophages. Indeed, neurodegeneration etiology is complex and yet to be completely understood, it may be that targeting TLRs could reveal a number of molecular and pharmacological aspects related to neurodegenerative diseases. Thus, activating TLR signaling modulation via natural resources could provide new therapeutic potentiality in the treatment of neurodegeneration.
神经元功能障碍会引发多种细胞内信号级联反应，释放不同的促炎细胞因子和趋化因子以及各种活性氧。除神经元外，小胶质细胞和星形胶质细胞也受到这种信号级联反应的影响。这种释放对细胞存活可能是有益的、中性的或有害的。 Toll 样受体 (TLR) 被激活并发出其下游信号通路以激活 NF-κB 和前 IL-1β，两者都负责神经炎症，并与不同与年龄相关的神经疾病的发病机制有关。然而，在这里，评估了多酚在治疗神经退行性疾病中的最新方面，重点是多酚对 TLR 的调节。不同的多酚类化合物，包括类黄酮、酚酸、酚醇、芪和木脂素，可能通过不同的途径靶向 TLR 信号。此外，一些多酚可以通过 TLR4/NF-κB/STAT 信号干预抑制炎症介质的过度表达，而另一些多酚可以通过调节小胶质细胞/巨噬细胞中的 TLR4/MyD88/NF-κB 通路来减少神经元凋亡。事实上，神经退行性变的病因很复杂，尚未完全了解，靶向 TLR 可能会揭示与神经退行性疾病相关的许多分子和药理学方面。因此，通过天然资源激活 TLR 信号调节可能为神经退行性疾病的治疗提供新的治疗潜力。
