Biological screening to identify hits the Therapeutic Targets of Alzheimer's disease and their role in the pathogenesis

Pooja Singh, Divya Sharma, Akanksha Singh, Himanshu Gupta, Arjun Singh
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Abstract

Alzheimer's disease (AD) is a major problem in today's societies. More than five million Americans are living with Alzheimer's disease in the United States, with the majority being 65 and older. According to the Alzheimer's Association Report, the number of persons affected by Alzheimer's disease in the United States would rise to fourteen million by 2060. The disease, which is the most prevalent form of dementia, is a progressive and irreversible brain disorder that gradually deteriorates an individual's cognitive function. It advances from preclinical to early- to moderate- to late-stage disease. Early symptoms primarily include cognitive impairment, particularly memory loss. Current Alzheimer's disease treatment can be divided into two categories based on the disease's stage. Galantamine, rivastigmine, and donepezil as acetylcholinesterase inhibitors are suitable for mild to moderate cases to provide transient symptomatic relief among patients. Memantine, an N-methyl D-aspartate (NMDA) antagonist, is used as monotherapy to treat symptoms of moderate to severe Alzheimer's disease. These medications are typically selective molecules that target certain proteins ("one compound-one target" method), and their main goal is to restore physiological acetylcholine levels. Nonetheless, multiple pathways of Alzheimer's disease pathogenesis have been hypothesized to far, and they have been proven to overlap and influence one another.
通过生物筛选确定阿尔茨海默病的治疗靶点及其在发病机制中的作用
阿尔茨海默病(AD)是当今社会的一个主要问题。在美国,有 500 多万美国人患有阿尔茨海默病,其中大多数是 65 岁及以上的老人。根据阿尔茨海默氏症协会的报告,到 2060 年,美国受阿尔茨海默氏症影响的人数将上升到一千四百万。阿尔茨海默氏症是痴呆症中最常见的一种,是一种渐进性、不可逆转的脑部疾病,会逐渐恶化患者的认知功能。它从临床前疾病发展为早期、中度到晚期疾病。早期症状主要包括认知障碍,尤其是记忆力减退。目前阿尔茨海默病的治疗可根据疾病的阶段分为两类。作为乙酰胆碱酯酶抑制剂的加兰他敏、利伐斯敏和多奈哌齐适用于轻度至中度病例,为患者提供短暂的症状缓解。美金刚是一种 N-甲基 D-天冬氨酸(NMDA)拮抗剂,可作为单一疗法用于治疗中度至重度阿尔茨海默病症状。这些药物通常是针对特定蛋白质的选择性分子("一化合物一靶点 "法),其主要目的是恢复乙酰胆碱的生理水平。然而,迄今为止,人们已经假设了阿尔茨海默病发病的多种途径,而且这些途径已被证明是相互重叠和相互影响的。
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