Joodi Sheer A, Ibrahim Weam W, Khattab Mahmoud M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, ElKasr Elaini Street, Cairo, 11562, Egypt.
Inflammopharmacology. 2025 Jan;33(1):195-214. doi: 10.1007/s10787-024-01608-7. Epub 2025 Jan 3.
The currently approved drugs for Alzheimer's disease (AD) are only for symptomatic treatment in the early stages of the disease but they could not halt the neurodegeneration, additionally, the safety profile of the recently developed immunotherapy is a big issue. This review aims to explain the importance of the drugs repurposing technique and strategy to develop therapy for AD. We illustrated the biological alterations in the pathophysiology of AD including the amyloid pathology, the Tau pathology, oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/β-catenin signaling, and autophagy. Additionally, we demonstrated the different repurposed drugs in the experimental models of AD including the anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant and anticancer drugs. Further, we showed the pipeline and FDA approved drugs for AD. The repurposed drugs have a promising therapeutic activity against AD, confirming the value of the drugs repurposing technique to elucidate curative therapy for AD.
目前已获批用于治疗阿尔茨海默病（AD）的药物仅用于该疾病早期的症状性治疗，但无法阻止神经退行性变。此外，最近开发的免疫疗法的安全性也是一个重大问题。本综述旨在解释药物重新利用技术和策略对于开发AD治疗方法的重要性。我们阐述了AD病理生理学中的生物学改变，包括淀粉样蛋白病理学、Tau病理学、氧化应激、线粒体功能障碍、神经炎症、谷氨酸介导的兴奋性毒性、胰岛素信号受损、无翅相关整合位点/β-连环蛋白信号传导和自噬。此外，我们展示了在AD实验模型中不同的重新利用药物，包括抗炎药、抗高血压药、抗糖尿病药、抗癫痫药、抗抑郁药和抗癌药。此外，我们还展示了用于AD的在研药物和美国食品药品监督管理局（FDA）批准的药物。重新利用的药物对AD具有有前景的治疗活性，证实了药物重新利用技术对于阐明AD治愈性疗法的价值。
