Type 2 diabetes mellitus and neurodegenerative disorders: The mitochondrial connection

IF 9.1 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological research Pub Date : 2024-09-30 DOI:10.1016/j.phrs.2024.107439
Isabella R. Baduini , Jose E. Castro Vildosola , Sheida Kavehmoghaddam , Fatmanur Kiliç , S. Aiman Nadeem , Juan J. Nizama , Marietta A. Rowand , Dileep Annapureddy , Chris-Ann Bryan , Lisa H. Do , Samuel Hsiao , Sai A. Jonnalagadda , Akhila Kasturi , Nikhila Mandava , Sachin Muppavaram , Bryan Ramirez , Aleece Siner , Christina N. Suoto , Nasira Tamajal , Ernest R. Scoma , Maria E. Solesio
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Abstract

The incidence of type 2 diabetes mellitus (T2DM) has increased in our society in recent decades as the population ages, and this trend is not expected to revert. This is the same for the incidence of the main neurodegenerative disorders, including the two most common ones, which are, Alzheimer’s and Parkinson’s disease. Currently, no pharmacological therapies have been developed to revert or cure any of these pathologies. Interestingly, in recent years, an increased number of studies have shown a high co-morbidity between T2DM and neurodegeneration, as well as some common molecular pathways that are affected in both types of diseases. For example, while the etiopathology of T2DM and neurodegenerative disorders is highly complex, mitochondrial dysfunction has been broadly described in the early steps of both diseases; accordingly, this dysfunction has emerged as a plausible molecular link between them. In fact, the prominent role played by mitochondria in the mammalian metabolism of glucose places the physiology of the organelle in a central position to regulate many cellular processes that are affected in both T2DM and neurodegenerative disorders. In this collaborative review, we critically describe the relationship between T2DM and neurodegeneration; making a special emphasis on the mitochondrial mechanisms that could link these diseases. A better understanding of the role of mitochondria on the etiopathology of T2DM and neurodegeneration could pave the way for the development of new pharmacological therapies focused on the regulation of the physiology of the organelle. These therapies could, ultimately, contribute to increase healthspan.
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2 型糖尿病与神经退行性疾病:线粒体的联系
近几十年来,随着人口老龄化的加剧,2 型糖尿病(T2DM)的发病率在我们的社会中不断上升,而且预计这一趋势不会逆转。主要神经退行性疾病的发病率也是如此,其中包括两种最常见的疾病,即阿尔茨海默病和帕金森病。目前,还没有研发出任何药物疗法来逆转或治愈这些病症。有趣的是,近年来越来越多的研究表明,T2DM 和神经退行性病变之间存在高度共病性,而且这两种疾病都会影响一些共同的分子通路。例如,虽然 T2DM 和神经退行性疾病的病因病理非常复杂,但线粒体功能障碍在这两种疾病的早期阶段就已被广泛描述;因此,线粒体功能障碍已成为这两种疾病之间的一种可信的分子联系。事实上,线粒体在哺乳动物的葡萄糖代谢过程中扮演着重要角色,这使得线粒体的生理学在调控 T2DM 和神经退行性疾病的许多细胞过程中处于核心地位。在这篇合作性综述中,我们对 T2DM 和神经退行性疾病之间的关系进行了批判性描述,并特别强调了将这些疾病联系在一起的线粒体机制。更好地了解线粒体在 T2DM 和神经退行性病变病因学中的作用,可为开发以调节细胞器生理机能为重点的新药物疗法铺平道路。这些疗法最终将有助于延长健康寿命。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacological research
Pharmacological research 医学-药学
CiteScore
18.70
自引率
3.20%
发文量
491
审稿时长
8 days
期刊介绍: Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.
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