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代谢组学和脂质组学在阿尔茨海默病药物发现中的最新进展。

Recent advances from metabolomics and lipidomics application in alzheimer's disease inspiring drug discovery.

机构信息

National Research Council, Digital Technologies Research Center, Ottawa, Canada.

Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, Canada.

出版信息

Expert Opin Drug Discov. 2020 Mar;15(3):319-331. doi: 10.1080/17460441.2020.1674808. Epub 2019 Oct 16.

Abstract

: Although age is a major risk factor for Alzheimer's disease (AD), it is not an inevitable consequence of aging nor is it exclusively an old-age disease. Several other major risk factors for AD are strongly associated with metabolism and include lack of exercise, obesity, diabetes, high blood pressure and cholesterol, over-consumption of alcohol and depression in addition to low educational level, social isolation, and cognitive inactivity. Approaches for Alzheimer prevention and treatment through manipulation of metabolism and utilization of active metabolites have great potential either as a primary or secondary treatment avenue or as a preventative strategy in high-risk individuals.: This review outlines the current knowledge concerning the relationship between AD and metabolism and the novel treatments attempting to correct changes in AD patients determined through metabolomics or lipidomic analyses.: Metabolites are one of the main driving factors and indicators of AD and can offer many possible avenues for prevention and treatment. However, with the highly interconnected effects of metabolites and metabolism, as well as the many different routes for metabolism dysfunction, successful treatment would have to include the correction of metabolic errors as well as errors in transport and metabolite processing in order to affect and revert AD progression.

摘要

尽管年龄是阿尔茨海默病(AD)的一个主要危险因素,但它不是衰老的必然结果,也不是老年病。AD 的其他几个主要危险因素与代谢密切相关,包括缺乏运动、肥胖、糖尿病、高血压和胆固醇、过度饮酒、抑郁,以及低教育水平、社会孤立和认知不活跃。通过代谢操纵和利用活性代谢物来预防和治疗 AD 的方法具有很大的潜力,可以作为主要或次要治疗途径,也可以作为高危人群的预防策略。

本文综述了目前关于 AD 与代谢之间关系的知识,以及试图通过代谢组学或脂质组学分析纠正 AD 患者变化的新治疗方法。

代谢物是 AD 的主要驱动因素和指标之一,为预防和治疗提供了许多可能的途径。然而,由于代谢物和代谢之间的高度相互关联的影响,以及代谢功能障碍的许多不同途径,成功的治疗方法必须包括纠正代谢错误以及运输和代谢物处理中的错误,以便影响和逆转 AD 的进展。

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