Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli, Uttar Pradesh, 226002, India.
Curr Med Chem. 2024;31(37):6032-6062. doi: 10.2174/0109298673264076230921065945.
Alzheimer's disease (AD) is a neurodegenerative disease and one of the leading causes of progressive dementia, affecting 50 million people worldwide. Many pathogenic processes, including amyloid β aggregation, tau hyperphosphorylation, oxidative stress, neuronal death, and deterioration of the function of cholinergic neurons, are associated with its progression. The one-compound-one-target treatment paradigm was unsuccessful in treating AD due to the multifaceted nature of Alzheimer's disease. The recent development of multitarget-directed ligand research has been explored to target the complementary pathways associated with the disease. We aimed to find the key role and progress of MTDLs in treating AD; thus, we searched for the past ten years of literature on "Pub- Med", "ScienceDirect", "ACS" and "Bentham Science" using the keywords neurodegenerative diseases, Alzheimer's disease, and multitarget-directed ligands. The literature was further filtered based on the quality of work and relevance to AD. Thus, this review highlights the current advancement and advantages of multitarget-directed ligands over traditional single-targeted drugs and recent progress in their development to treat AD.
阿尔茨海默病（AD）是一种神经退行性疾病，也是进行性痴呆的主要原因之一，全球有 5000 万人受到影响。许多发病机制，包括淀粉样β聚集、tau 过度磷酸化、氧化应激、神经元死亡以及胆碱能神经元功能恶化，都与疾病的进展有关。由于阿尔茨海默病的多面性，一种化合物针对一个靶点的治疗模式在治疗 AD 方面并不成功。最近已经探索了多靶点配体药物的研究，以针对与疾病相关的互补途径。我们旨在找到 MTDLs 在治疗 AD 中的关键作用和进展；因此，我们使用“Pub-Med”、“ScienceDirect”、“ACS”和“Bentham Science”上过去十年的文献，使用关键词神经退行性疾病、阿尔茨海默病和多靶点配体药物进行了搜索。根据工作质量和与 AD 的相关性，对文献进行了进一步筛选。因此，本综述强调了多靶点配体药物相对于传统的单靶点药物的最新进展及其在治疗 AD 方面的开发进展。
