Sharma Amit, Rudrawar Santosh, Bharate Sandip B, Jadhav Hemant R
Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Sciences Pilani Pilani Campus, Vidya Vihar Pilani 333031 RJ India
The Institute for Biomedicine and Glycomics, Griffith University Gold Coast 4222 Australia.
RSC Med Chem. 2024 Dec 6;16(2):652-693. doi: 10.1039/d4md00630e. eCollection 2025 Feb 19.
Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology. The developmental drugs target pivotal disease factors involved in the envisaged hypotheses and include targets such as amyloid aggregation, hyperphosphorylated tau proteins, and receptors like cholinergic, adrenergic, Present-day research focuses on multi-target directed ligands (MTDLs), which inhibit multiple factors simultaneously, helping slow the disease's progression. This review attempts to collate the recent information related to proposed hypotheses for AD etiology. It systematically organizes the advances in various therapeutic options for AD, with a particular emphasis on clinical candidates. Also, it is expected to help medicinal chemists design novel AD treatments based on available information, which could be helpful to AD patients.
阿尔茨海默病（AD）是一种复杂的、无法治愈的神经疾病，其特征为认知衰退、胆碱能神经元减少和神经元丢失。其确切病理仍不确定，但已出现多种治疗假说。目前的治疗方法，无论是单一治疗还是联合治疗，都只能缓解症状，由于其病理的多面性，难以有效控制AD。正在研发的药物针对设想假说中涉及的关键疾病因素，包括淀粉样蛋白聚集、过度磷酸化的tau蛋白等靶点，以及胆碱能、肾上腺素能等受体。当今的研究集中在多靶点导向配体（MTDLs）上，它们能同时抑制多种因素，有助于减缓疾病进展。本综述试图整理与AD病因学提出的假说相关的最新信息。它系统地梳理了AD各种治疗选择的进展，特别强调临床候选药物。此外，有望帮助药物化学家根据现有信息设计新型AD治疗方法，这可能对AD患者有益。
