Alzheimer's disease (AD) is a detrimental neurodegenerative disease affecting the elderly. Clinically, it is characterized by progressive memory decline and subsequent loss of broader cognitive functions. Current drugs provide only symptomatic relief but do not have profound disease-modifying effects. There is an unmet need to identify novel pharmacological agents for AD therapy. Neuropathologically, the characteristic hallmarks of the disease are extracellular senile plaques containing amyloid β-peptides and intracellular neurofibrillary tangles containing hyperphosphorylated microtubule-associated protein tau. Simultaneously, oxidative stress, neuroinflammation and mitochondrial dysfunction in specific brain regions are early events during the process of AD pathologic changes and are associated with Aβ/tau toxicity. Here, we first summarized probable pathogenic mechanisms leading to neurodegeneration and hopefully identify pathways that serve as specific targets to improve therapy for AD. We then reviewed the mechanisms that underlie disease-modifying effects of natural polyphenols, with a focus on nuclear factor erythroid 2-related factor 2 activators for AD treatment. Lastly, we discussed challenges in the preclinical to clinical translation of natural polyphenols. In conclusion, there is evidence that natural polyphenols can be therapeutically useful in AD through their multifaceted mechanism of action. However, more clinical studies are needed to confirm these effects.

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天然多酚：其针对阿尔茨海默病发病机制的治疗潜力

阿尔茨海默病（AD）是一种影响老年人的有害神经退行性疾病。临床上，其特征是进行性记忆衰退和随后丧失更广泛的认知功能。目前的药物只能缓解症状，但没有深远的疾病缓解作用。寻找用于 AD 治疗的新型药物制剂的需求尚未得到满足。在神经病理学上，该疾病的特征性标志是含有淀粉样β肽的细胞外老年斑和含有过度磷酸化微管相关蛋白tau的细胞内神经原纤维缠结。同时，特定脑区的氧化应激、神经炎症和线粒体功能障碍是AD病理变化过程中的早期事件，并与Aβ/tau毒性相关。在这里，我们首先总结了导致神经退行性变的可能致病机制，并希望找出作为改善 AD 治疗的特定靶点的途径。然后，我们回顾了天然多酚缓解疾病作用的机制，重点关注用于 AD 治疗的核因子红细胞 2 相关因子 2 激活剂。最后，我们讨论了天然多酚的临床前转化为临床的挑战。总之，有证据表明天然多酚可以通过其多方面的作用机制在治疗 AD 方面发挥作用。然而，需要更多的临床研究来证实这些效果。