Cognitive dysfunction can occur both in normal aging and age-related neurological disorders, such as mild cognitive impairment and Alzheimer's disease (AD). These disorders have few treatment options due to side effects and limited efficacy. New approaches to slow cognitive decline are urgently needed. Dietary interventions (nutraceuticals) have received considerable attention because they exhibit strong neuroprotective properties and may help prevent or minimize AD symptoms. Biological aging is driven by a series of interrelated mechanisms, including oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy, which function through various signaling pathways. Recent clinical and preclinical studies have shown that dietary small molecules derived from natural sources, including flavonoids, carotenoids, and polyphenolic acids, can modulate oxidative damage, cognitive impairments, mitochondrial dysfunction, neuroinflammation, neuronal apoptosis, autophagy dysregulation, and gut microbiota dysbiosis. This paper reviews research on different dietary small molecules and their bioactive constituents in the treatment of AD. Additionally, the chemical structure, effective dose, and specific molecular mechanisms of action are comprehensively explored. This paper also discusses the advantages of using nanotechnology-based drug delivery, which significantly enhances oral bioavailability, safety, and therapeutic effect, and lowers the risk of adverse effects. These agents have considerable potential as novel and safe therapeutic agents that can prevent and combat age-related AD.

中文翻译：

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开发膳食小分子作为阿尔茨海默病的多靶点治疗策略


认知功能障碍可能发生在正常衰老和与年龄相关的神经系统疾病中，例如轻度认知障碍和阿尔茨海默病（AD）。由于副作用和疗效有限，这些疾病的治疗选择很少。迫切需要减缓认知能力下降的新方法。饮食干预（营养保健品）受到了相当多的关注，因为它们具有很强的神经保护特性，可能有助于预防或减轻 AD 症状。生物衰老是由一系列相互关联的机制驱动的，包括氧化应激、神经炎症、神经元凋亡和自噬，这些机制通过各种信号通路发挥作用。最近的临床和临床前研究表明，源自天然来源的膳食小分子，包括类黄酮、类胡萝卜素和多酚酸，可以调节氧化损伤、认知障碍、线粒体功能障碍、神经炎症、神经元凋亡、自噬失调和肠道微生物群失调。本文综述了不同膳食小分子及其生物活性成分在 AD 治疗中的研究。此外，还全面探讨了化学结构、有效剂量和具体的分子作用机制。本文还讨论了使用基于纳米技术的药物递送的优点，它显着提高了口服生物利用度、安全性和治疗效果，并降低了不良反应的风险。这些药物作为新型、安全的治疗药物具有巨大的潜力，可以预防和对抗与年龄相关的 AD。