Department of Biology and Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, USA.
Department of Biology and Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, USA.
Pharmacol Res. 2024 Nov;209:107439. doi: 10.1016/j.phrs.2024.107439. Epub 2024 Sep 30.
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.
近年来，随着人口老龄化，2 型糖尿病（T2DM）的发病率在我们的社会中有所增加，而且这种趋势预计不会逆转。主要神经退行性疾病的发病率也是如此，包括两种最常见的疾病，即阿尔茨海默病和帕金森病。目前，还没有开发出任何药物疗法来逆转或治愈这些疾病。有趣的是，近年来，越来越多的研究表明 T2DM 和神经退行性变之间存在高度的共病性，以及一些在这两种疾病中都受到影响的共同分子途径。例如，虽然 T2DM 和神经退行性疾病的病因发病机制非常复杂，但线粒体功能障碍在这两种疾病的早期阶段都得到了广泛描述；因此，这种功能障碍已经成为它们之间的一个合理的分子联系。事实上，线粒体在哺乳动物葡萄糖代谢中的突出作用使细胞器的生理学处于调节许多在 T2DM 和神经退行性疾病中受到影响的细胞过程的核心位置。在这篇合作评论中，我们批判性地描述了 T2DM 和神经退行性变之间的关系；特别强调了可能将这些疾病联系起来的线粒体机制。更好地理解线粒体在 T2DM 和神经退行性变的病因发病机制中的作用，可能为开发新的药物疗法铺平道路，这些疗法侧重于调节细胞器的生理学。这些疗法最终可能有助于增加健康寿命。
