Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.
Department of Biochemistry and Biotechnology, Faculty of Medicine and Life Sciences, University Rovira i Virgili, Reus, Spain.
Curr Pharm Des. 2020;26(12):1286-1299. doi: 10.2174/1381612826666200211121416.
Late-onset Alzheimer's disease (LOAD) is a neurodegenerative disorder that has become a worldwide health problem. This pathology has been classically characterized for its affectation on cognitive function and the presence of depositions of extracellular amyloid β-protein (Aβ) and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein. To this day, no effective treatment has been developed. Multiple strategies have been proposed over the years with the aim of finding new therapeutic approaches, such as the sequestration of Aβ in plasma or the administration of anti-inflammatory drugs. Also, given the significant role of the insulin receptor in the brain in the proper maintenance of cognitive function, drugs focused on the amelioration of insulin resistance have been proposed as potentially useful and effective in the treatment of AD. In the present review, taking into account the molecular complexity of the disease, it has been proposed that the most appropriate therapeutic strategy is a combinatory treatment of several drugs that will regulate a wide spectrum of the described altered pathological pathways.
迟发性阿尔茨海默病（LOAD）是一种神经退行性疾病，已成为全球健康问题。这种病理学以前以其对认知功能的影响以及细胞外淀粉样β-蛋白（Aβ）和由过度磷酸化 Tau 蛋白组成的细胞内神经原纤维缠结（NFT）的沉积为特征。直到今天，还没有开发出有效的治疗方法。多年来提出了多种策略，旨在寻找新的治疗方法，例如在血浆中隔离 Aβ或使用抗炎药物。此外，鉴于胰岛素受体在大脑中对认知功能的正常维持中具有重要作用，因此针对改善胰岛素抵抗的药物被认为在 AD 的治疗中具有潜在的有用性和有效性。在本综述中，考虑到疾病的分子复杂性，已经提出最适当的治疗策略是联合使用几种药物进行治疗，这将调节所描述的广泛病理途径的改变。
