iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal.
iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade NOVA de Lisboa, Avenida da República, Oeiras, Portugal; iBET, Instituto de Biologia Experimental e Tecnológica, Avenida da República, Apartado 12, Oeiras, Portugal.
Neurochem Int. 2024 Oct;179:105836. doi: 10.1016/j.neuint.2024.105836. Epub 2024 Aug 14.
Neurodegenerative diseases (NDDs) are an increasing group of chronic and progressive neurological disorders that ultimately lead to neuronal cell failure and death. Despite all efforts throughout decades, their burden on individuals and society still casts one of the most massive socioeconomic problems worldwide. The neuronal failure observed in NDDs results from an intricacy of events, mirroring disease complexity, ranging from protein aggregation, oxidative stress, (neuro)inflammation, and even blood-brain barrier (BBB) dysfunction, ultimately leading to cognitive and motor symptoms in patients. As a result of such complex pathobiology, to date, there are still no effective treatments to treat/halt NDDs progression. Fortunately, interest in the bioavailable low molecular weight (LMW) phenolic metabolites derived from the metabolism of dietary (poly)phenols has been rising due to their multitargeted potential in attenuating multiple NDDs hallmarks. Even if not highly BBB permeant, their relatively high concentrations in the bloodstream arising from the intake of (poly)phenol-rich diets make them ideal candidates to act within the vasculature and particularly at the level of BBB. In this review, we highlight the most recent - though still scarce - studies demonstrating LMW phenolic metabolites' ability to modulate BBB homeostasis, including the improvement of tight and adherens junctional proteins, as well as their power to decrease pro-inflammatory cytokine secretion and oxidative stress levels in vitro and in vivo. Specific BBB-permeant LMW phenolic metabolites, such as simple phenolic sulfates, have been emerging as strong BBB properties boosters, pleiotropic compounds capable of improving cell fitness under oxidative and pro-inflammatory conditions. Nevertheless, further studies should be pursued to obtain a holistic overview of the promising role of LMW phenolic metabolites in NDDs prevention and management to fully harness their true therapeutic potential.
神经退行性疾病（NDDs）是一组不断增加的慢性和进行性神经障碍，最终导致神经元细胞衰竭和死亡。尽管几十年来一直在努力，但它们给个人和社会带来的负担仍然是全球最严重的社会经济问题之一。NDDs 中观察到的神经元衰竭是一系列复杂事件的结果，反映了疾病的复杂性，从蛋白质聚集、氧化应激、（神经）炎症，甚至血脑屏障（BBB）功能障碍，最终导致患者出现认知和运动症状。由于这种复杂的病理生物学，迄今为止，仍然没有有效的治疗方法来治疗/阻止 NDDs 的进展。幸运的是，由于其在减轻多种 NDDs 特征方面的多靶点潜力，源自膳食（多）酚代谢的生物可利用低分子量（LMW）酚类代谢物的兴趣日益增加。即使它们不能很好地穿透 BBB，由于富含（多）酚的饮食摄入，它们在血液中的相对高浓度使它们成为在血管内，特别是在 BBB 水平发挥作用的理想候选物。在这篇综述中，我们强调了最近的——尽管仍然很少——研究表明 LMW 酚类代谢物调节 BBB 稳态的能力，包括改善紧密和黏附连接蛋白，以及它们降低体外和体内促炎细胞因子分泌和氧化应激水平的能力。特定的 BBB 可渗透的 LMW 酚类代谢物，如简单的酚硫酸盐，已成为增强 BBB 特性的强大化合物，是能够在氧化和促炎条件下提高细胞适应性的多效化合物。然而，应该进行进一步的研究，以全面了解 LMW 酚类代谢物在 NDDs 预防和管理中的有前途的作用，以充分发挥其真正的治疗潜力。
