Department of Pharmacognosy, School of Pharmacy, China Medical University, Shenyang, China.
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
Eur J Med Chem. 2021 Jun 5;218:113401. doi: 10.1016/j.ejmech.2021.113401. Epub 2021 Mar 27.
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by neuronal loss and cognitive impairment that harshly affect the elderly individuals. Currently, the available anti-AD pharmacological approaches are purely symptomatic to alleviate AD symptoms, and the curative effects of novel anti-AD drugs focused on Aβ target are disappointing. Hence, there is a tremendous need to adjust AD therapeutic targets and discover novel anti-AD agents. In AD, mitochondrial dysfunction gradually triggers neuronal death from different aspects and worsens the occurrence and progress of AD. Consequently, it has been proposed that the intervention of impaired mitochondria represents an attractive breakthrough point for AD treatments. Due to chemical diversity, poly-pharmacological activities, few adverse effects and multiple targeting, natural products (NPs) have been identified as a valuable treasure for drug discovery and development. Multiple lines of studies have scientifically proven that NPs display ameliorative benefits in AD treatment in relation to mitochondrial dysfunction. This review surveys the complicated implications for mitochondrial dysregulation and AD, and then summarizes the potentials of NPs and their underlying molecular mechanisms against AD via reducing or improving mitochondrial dysfunction. It is expected that this work may open the window to speed up the development of innovative anti-AD drugs originated from NPs and improve upcoming AD therapeutics.
阿尔茨海默病（AD）是最常见的进行性神经退行性疾病，其特征是神经元丧失和认知障碍，严重影响老年人。目前，可用的抗 AD 药物治疗方法纯粹是对症治疗，以减轻 AD 症状，而新型抗 AD 药物聚焦于 Aβ 靶点的疗效令人失望。因此，迫切需要调整 AD 的治疗靶点并发现新型的抗 AD 药物。在 AD 中，线粒体功能障碍逐渐从不同方面引发神经元死亡，并使 AD 的发生和发展恶化。因此，有人提出，干预受损的线粒体代表了 AD 治疗的一个有吸引力的突破点。由于化学多样性、多药理学活性、很少的不良反应和多靶向性，天然产物（NPs）已被确定为药物发现和开发的宝贵资源。多项研究科学证明，NPs 在与线粒体功能障碍相关的 AD 治疗中显示出改善作用。本综述调查了线粒体失调与 AD 的复杂关系，然后总结了 NPs 及其潜在的分子机制通过减少或改善线粒体功能障碍对 AD 的潜在作用。希望这项工作可以为源于 NPs 的创新型抗 AD 药物的开发开辟道路，并改善未来的 AD 治疗方法。
