PDF(Pubmed)
Abstract：
The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell\'s intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.
摘要：
神经系统疾病的发病率，特别是年龄相关的神经退行性病变，呈现出惊人的上升趋势，而目前的药物干预很少达到治愈效果。尽管他们的临床表现不同，神经系统疾病通常具有共同的病理线索：内质网（ER）内错误折叠蛋白的异常积累。这种现象,被称为ER压力，当细胞的内在质量控制机制无法应对蛋白质折叠负担时，就会出现这种情况。因此,错误折叠的蛋白质在内质网腔中积累，触发细胞应激反应的级联。认识到这一挑战，在过去的二十年中，研究人员加大了努力，以探索可能减缓甚至逆转这些破坏性疾病的天然化合物。黄酮类化合物构成了浩瀚且异质的一类植物多酚，超过10,000个来自不同的天然来源，如葡萄酒，蔬菜,药用植物,有机产品。黄酮类化合物通常分为六个不同的亚类：花青素，黄烷酮,黄酮,黄酮醇，异黄酮,和黄酮醇。不同的类黄酮家族，具有一个常见的酚环骨架装饰有不同的羟基和额外的修饰，通过抑制ROS的形成发挥其抗氧化活性，研究证明了这一点。此外，研究表明,类黄酮等多酚可通过凋亡和自噬调节内质网应激。通过了解这些机制，我们可以释放黄酮类化合物作为神经退行性疾病新型治疗剂的潜力。因此,这篇综述严格审查了文献，探索黄酮类化合物对神经系统疾病中ER应激的各个步骤的调节作用。
