Department of Biochemistry and Physiology, Physiology Section, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Laboratory of Cellular and Molecular Pathology, Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, 3460000 Talca, Chile.
Front Biosci (Landmark Ed). 2022 May 6;27(5):146. doi: 10.31083/j.fbl2705146.
The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.
人口老龄化和增长的增加导致了痴呆症患者人数的增加，阿尔茨海默病（AD）是最常见的原因。尽管数十年来进行了密集的研究，但尚未找到治疗 AD 的方法。然而，已经提出了一些可能改变疾病进展并有助于控制症状的治疗方法。除了 AD 发病机制的经典假说，即β淀粉样肽（Aβ）积累和 tau 过度磷酸化外，将其他分子机制归因于关键作用的趋势促使人们研究不同的治疗靶点。因此，旨在调节炎症、胰岛素抵抗、突触、神经发生、心血管因素和菌群失调的药物正在为 AD 治疗开辟新的前景。在这一框架内，预计用于疾病修饰治疗的候选药物数量将会增加，并且还将关注可能的组合多药物策略。本综述总结了针对 Aβ和 tau 的药物的最新进展，这两种物质是 AD 病理生理学的主要贡献者。此外，它还介绍了在临床研究中针对被认为参与 AD 神经退行性过程的替代机制的最重要药物。
