Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Drug Clinical Trial Research Center, China-Japan Friendship Hospital, Beijing, 100029, China.
Curr Top Med Chem. 2019;19(3):187-204. doi: 10.2174/1568026619666190201153257.
Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.
阿尔茨海默病（AD）是一种进行性和致命的神经退行性疾病，其特征是记忆丧失、认知障碍和痴呆。在过去几十年中，根据 AD 患者大脑的病理变化，提出了几种发病机制假说。不幸的是，目前尚无有效的药物/疗法可以预防或控制 AD。目前，只有少数几种药物可用，这些药物的作用是乙酰胆碱酯酶（AChE）抑制剂或 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可缓解症状。由于许多小分子天然产物在中枢神经系统（CNS）药物的开发过程中表现出作为受体激动剂或拮抗剂以及脑内酶和蛋白质抑制剂的功能，因此天然产物很可能在抗 AD 药物开发中发挥重要作用。我们回顾了最近关于使用小分子天然产物作为治疗 AD 的药物候选物的论文。这些天然产物具有抗氧化、抗炎、抗胆碱酯酶、抗淀粉样变性和神经保护作用。此外，还总结了用于预防 AD、减轻 AD 症状以及 AD 治疗新靶点的有生物活性的天然产物。
