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阿尔茨海默病的治疗方法:代谢角度。

Therapies for Alzheimer's disease: a metabolic perspective.

机构信息

Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal.

Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra 3000-548, Portugal.

出版信息

Mol Genet Metab. 2021 Mar;132(3):162-172. doi: 10.1016/j.ymgme.2021.01.011. Epub 2021 Jan 27.

Abstract

Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly. Currently, there are over 50 million cases of dementia worldwide and it is expected that it will reach 136 million by 2050. AD is described as a neurodegenerative disease that gradually compromises memory and learning capacity. Patients often exhibit brain glucose hypometabolism and are more susceptible to develop type 2 diabetes or insulin resistance in comparison with age-matched controls. This suggests that there is a link between both pathologies. Glucose metabolism and the tricarboxylic acid cycle are tightly related to mitochondrial performance and energy production. Impairment of both these pathways can evoke oxidative damage on mitochondria and key proteins linked to several hallmarks of AD. Glycation is also another type of post-translational modification often reported in AD, which might impair the function of proteins that participate in metabolic pathways thought to be involved in this illness. Despite needing further research, therapies based on insulin treatment, usage of anti-diabetes drugs or some form of dietary intervention, have shown to be promising therapeutic approaches for AD in its early stages of progression and will be unveiled in this paper.

摘要

阿尔茨海默病(AD)是老年人中最常见的痴呆症形式之一。目前,全球有超过 5000 万人患有痴呆症,预计到 2050 年将达到 1.36 亿。AD 被描述为一种神经退行性疾病,它逐渐损害记忆和学习能力。与年龄匹配的对照组相比,患者经常表现出大脑葡萄糖代谢低下,并且更容易患上 2 型糖尿病或胰岛素抵抗。这表明这两种病理之间存在联系。葡萄糖代谢和三羧酸循环与线粒体功能和能量产生密切相关。这两种途径的损伤都会引起线粒体和与 AD 的几个特征相关的关键蛋白的氧化损伤。糖化作用也是 AD 中经常报道的另一种翻译后修饰类型,它可能会损害参与代谢途径的蛋白质的功能,这些代谢途径被认为与这种疾病有关。尽管需要进一步研究,但基于胰岛素治疗、使用抗糖尿病药物或某种饮食干预的疗法已被证明是 AD 早期进展阶段有前途的治疗方法,本文将对此进行探讨。

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