Peng Yong, Jin Hong, Xue Ya-Hui, Chen Quan, Yao Shun-Yu, Du Miao-Qiao, Liu Shu
Neurology Department, The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan, China.
Neurology Department, The Third Affiliated Hospital of Hunan University of Chinese Medicine, Zhuzhou, Hunan, China.
Front Aging Neurosci. 2023 Aug 3;15:1206572. doi: 10.3389/fnagi.2023.1206572. eCollection 2023.
Alzheimer's disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients' families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.
阿尔茨海默病（AD）是全球最常见的慢性神经退行性疾病。它会导致认知功能障碍，如失语症和失认症，以及精神症状，如行为异常；所有这些都给患者家庭带来了巨大的心理和经济负担。目前尚无治疗AD的特效药物，现有的AD药物只能延缓疾病的发作和进展。AD的病理生理基础涉及β-淀粉样蛋白（Aβ）异常沉积、tau蛋白异常磷酸化、乙酰胆碱含量活性降低、谷氨酸毒性、自噬、炎症反应、线粒体靶向作用以及多靶点作用。美国食品药品监督管理局（FDA）已批准五种药物用于临床：他克林、多奈哌齐、卡巴拉汀、加兰他敏、美金刚和仑卡奈单抗。我们关注的是那些已经历临床试验的新型药物，其中大多数由于临床副作用过大或疗效不佳而未获成功。尽管阿杜卡单抗于2021年6月7日迅速获得了FDA的批准，但其长期安全性和耐受性仍需进一步监测和确认。在这篇文献综述中，我们旨在探讨AD发生和发展背后可能的病理生理机制。我们重点关注抗Aβ和抗tau药物、线粒体靶向和多靶点药物、市售药物、药物研发中遇到的瓶颈以及未来药物研发可能的靶点和治疗策略。我们希望为未来AD的药物治疗提出新的概念和方法。
