Alzheimer’s disease (AD) is a progressive and degenerative brain disorder that has emerged as one of the major public health problems in adults. Unfortunately, its molecular pathology and therapeutic strategies remain elusive. Because there are multiple factors closely indicated in the pathogenesis of AD, multiple drug therapy will be required to address the varied pathological aspects of this disease. Existing pharmacological approaches with one-molecule-one-target are limited in their ability to modify the pathology of AD. Novel therapeutics strategies comprise multifunctional compounds specifically designed to target concurrently on different sites at multifactorial etiopathogenesis of AD, thereby providing greater therapeutic efficacy. Over the past decade, our group has developed several series of dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and huperzine A, a unique anti-Alzheimer’s drug originally discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor, nitric oxide synthase, and amyloid precursor protein/β-amyloid cascade concurrently, possesses remarkable neuroprotective activities. More importantly, the synergism between these targets might serve as one of the most effective therapeutic strategies to arrest/modify pathological process of AD in addition to improving the cognitive functions for AD.

中文翻译：

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新型抗阿尔茨海默病二聚体 Bis(7)-cognitin：通过多个靶点实现神经保护的细胞和分子机制。


阿尔茨海默病（AD）是一种进行性和退行性脑部疾病，已成为成年人的主要公共卫生问题之一。不幸的是，其分子病理学和治疗策略仍然难以捉摸。由于 AD 的发病机制密切表明多种因素，因此需要多种药物治疗来解决该疾病的不同病理方面。现有的一分子一靶点药理学方法改变​​ AD 病理的能力有限。新型治疗策略包括专门设计用于同时靶向 AD 多因素发病机制的不同部位的多功能化合物，从而提供更大的治疗功效。过去十年，我们课题组以他克林和石杉碱甲为原料，开发了多个系列的二聚乙酰胆碱酯酶（AChE）抑制剂。石杉碱甲是一种独特的抗阿尔茨海默病药物，最初是从传统中药植物中发现的。 Bis(7)-Cognitin 是我们的新型二聚体之一，通过同时抑制 AChE、N-甲基-D-天冬氨酸受体、一氧化氮合酶和淀粉样前体蛋白/β-淀粉样蛋白级联，具有显着的神经保护活性。更重要的是，除了改善AD的认知功能外，这些靶点之间的协同作用可能成为阻止/改变AD病理过程的最有效的治疗策略之一。