Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi 110042, India.
Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi 110042, India.
Biochim Biophys Acta Mol Basis Dis. 2017 May;1863(5):1132-1146. doi: 10.1016/j.bbadis.2016.06.015. Epub 2016 Jun 21.
Mounting evidence suggests a link between metabolic syndrome (MetS) such as diabetes, obesity, non-alcoholic fatty liver disease in the progression of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDDs). For instance, accumulated Aβ oligomer is enhancing neuronal Ca release and neural NO where increased NO level in the brain through post translational modification is modulating the level of insulin production. It has been further confirmed that irrespective of origin; brain insulin resistance triggers a cascade of the neurodegeneration phenomenon which can be aggravated by free reactive oxygen species burden, ER stress, metabolic dysfunction, neuorinflammation, reduced cell survival and altered lipid metabolism. Moreover, several studies confirmed that MetS and diabetic sharing common mechanisms in the progression of AD and NDDs where mitochondrial dynamics playing a critical role. Any mutation in mitochondrial DNA, exposure of environmental toxin, high-calorie intake, homeostasis imbalance, glucolipotoxicity is causative factors for mitochondrial dysfunction. These cumulative pleiotropic burdens in mitochondria leads to insulin resistance, increased ROS production; enhanced stress-related enzymes that is directly linked MetS and diabetes in neurodegeneration. Since, the linkup mechanism between mitochondrial dysfunction and disease phenomenon of both MetS and NDDs is quite intriguing, therefore, it is pertinent for the researchers to identify and implement the therapeutic interventions for targeting MetS and NDDs. Herein, we elucidated the pertinent role of MetS induced mitochondrial dysfunction in neurons and their consequences in NDDs. Further, therapeutic potential of well-known biomolecules and chaperones to target altered mitochondria has been comprehensively documented. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.
越来越多的证据表明，代谢综合征（如糖尿病、肥胖症、非酒精性脂肪性肝病）与阿尔茨海默病（AD）、帕金森病（PD）和其他神经退行性疾病（NDDs）的进展之间存在关联。例如，积累的 Aβ 寡聚体增强神经元 Ca 释放和神经 NO，而大脑中 NO 水平的增加通过翻译后修饰调节胰岛素的产生水平。进一步证实，无论起源如何；脑胰岛素抵抗引发神经退行性病变的级联反应，而自由基应激、内质网应激、代谢功能障碍、神经炎症、细胞存活减少和脂质代谢改变等可加重这种级联反应。此外，有几项研究证实，代谢综合征和糖尿病在 AD 和 NDDs 的进展中具有共同的机制，其中线粒体动力学起着关键作用。线粒体 DNA 的任何突变、环境毒素的暴露、高热量摄入、内环境失衡、糖脂毒性都是线粒体功能障碍的原因。这些累积的多效性线粒体负担导致胰岛素抵抗、ROS 产生增加；增强与应激相关的酶，这与神经退行性变中的代谢综合征和糖尿病直接相关。由于线粒体功能障碍与代谢综合征和 NDDs 两种疾病现象之间的联系机制非常有趣，因此，研究人员识别并实施针对代谢综合征和 NDDs 的治疗干预措施是非常重要的。本文阐述了代谢综合征诱导的神经元中线粒体功能障碍的相关作用及其在 NDDs 中的后果。此外，还全面记录了众所周知的生物分子和分子伴侣靶向改变的线粒体的治疗潜力。本文是题为“氧化应激和糖尿病/肥胖症及疾病谱危重疾病中的线粒体质量”的特刊的一部分，由 P. Hemachandra Reddy 编辑。
