Departamento de Quimica Organica y Fisicoquimica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Olivos 1007, Independencia, Santiago, Chile.
Curr Neuropharmacol. 2021;19(6):832-867. doi: 10.2174/1570159X18666200914155951.
Alzheimer's disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous AD-related targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted in being inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well established and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy.
阿尔茨海默病（AD）是一种慢性、进行性和致命的神经退行性疾病，影响认知、行为和功能，是老年人精神恶化的最常见原因之一。过去认为 AD 只是由于β淀粉样蛋白沉积或神经纤维缠结引起的，但在过去几十年中，已经确定了许多与 AD 相关的靶点，AD 的多因素性质变得明显。在这种情况下，一种药物-一种靶点的范式在应对 AD 和其他具有复杂病因的疾病方面效率低下，为多靶点方法的出现开辟了道路。在这篇综述中，我们强调了该领域的最新进展，重点介绍了具有与 AD 相关药理学特性的知名化学支架的杂交工具，如姜黄素、白藜芦醇、色酮和吲哚。我们主要关注已确立和初期的 AD 治疗靶点，如乙酰胆碱酯酶、丁酰胆碱酯酶、单胺氧化酶、β-淀粉样蛋白沉积、5-HT4 和 5-羟色胺转运体，旨在为 AD 的多靶点治疗提供新的见解。
