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Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential
Medicinal Research Reviews ( IF 13.3 ) Pub Date : 2017-04-19 , DOI: 10.1002/med.21440 Ana Marta de Matos 1, 2 , Maria Paula de Macedo 2 , Amélia Pilar Rauter 1
Medicinal Research Reviews ( IF 13.3 ) Pub Date : 2017-04-19 , DOI: 10.1002/med.21440 Ana Marta de Matos 1, 2 , Maria Paula de Macedo 2 , Amélia Pilar Rauter 1
Affiliation
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age‐related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients. This review provides an update on overlapping pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity, and even shared genetic background. These events will be presented as puzzle pieces put together, thus establishing potential therapeutic targets for drug discovery and development against T2D and diabetes‐induced cognitive decline—a heavyweight contributor to the increasing incidence of dementia in developed countries. Hoping to pave the way in this direction, we will present some of the most promising and well‐studied drug leads with potential against both pathologies, including their respective bioactivity reports, mechanisms of action, and structure–activity relationships.
中文翻译:
桥接2型糖尿病和阿尔茨海默氏病:寻求具有治疗和预防潜力的分子拼装拼图
2型糖尿病(T2D)和阿尔茨海默氏病(AD)是两种与年龄有关的淀粉样变性病,影响了全球数百万人。在流行病学数据的广泛支持下,2型糖尿病患者中AD的较高发病率导致T2D被认为是AD发生的有形危险因素。确实,现在有越来越多的证据表明脑胰岛素抵抗和缺乏引起的脑结构和功能异常,最终凸显了对能够预防2型糖尿病患者发展AD的新方法的需求。这篇综述提供了有关T2D和AD中重叠的病理生理机制和途径的更新,例如淀粉样蛋白生成事件,氧化应激,内皮功能障碍,异常的酶活性,甚至共有的遗传背景。这些事件将以拼图形式呈现,从而为针对T2D和糖尿病引起的认知能力下降的药物发现和开发建立潜在的治疗目标,这是发达国家痴呆症发病率不断增加的重要因素。为了给这个方向铺平道路,我们将介绍一些最有前途和经过充分研究的潜在药物,它们有可能针对两种病理,包括它们各自的生物活性报告,作用机理以及结构-活性关系。
更新日期:2017-04-19
中文翻译:
桥接2型糖尿病和阿尔茨海默氏病:寻求具有治疗和预防潜力的分子拼装拼图
2型糖尿病(T2D)和阿尔茨海默氏病(AD)是两种与年龄有关的淀粉样变性病,影响了全球数百万人。在流行病学数据的广泛支持下,2型糖尿病患者中AD的较高发病率导致T2D被认为是AD发生的有形危险因素。确实,现在有越来越多的证据表明脑胰岛素抵抗和缺乏引起的脑结构和功能异常,最终凸显了对能够预防2型糖尿病患者发展AD的新方法的需求。这篇综述提供了有关T2D和AD中重叠的病理生理机制和途径的更新,例如淀粉样蛋白生成事件,氧化应激,内皮功能障碍,异常的酶活性,甚至共有的遗传背景。这些事件将以拼图形式呈现,从而为针对T2D和糖尿病引起的认知能力下降的药物发现和开发建立潜在的治疗目标,这是发达国家痴呆症发病率不断增加的重要因素。为了给这个方向铺平道路,我们将介绍一些最有前途和经过充分研究的潜在药物,它们有可能针对两种病理,包括它们各自的生物活性报告,作用机理以及结构-活性关系。