Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Curr Mol Med. 2013 May;13(4):586-601. doi: 10.2174/1566524011313040010.
Diabetes mellitus is one of the most prevalent chronic diseases. Since glucose is the main fuel of the brain, its levels should be maintained within a narrow range to ensure normal brain function. Indeed, the literature shows that uncontrolled blood glucose levels, whether too high or too low, impact brain structure and function potentiating cognitive impairment. Uncoupling proteins (UCPs) are a family of mitochondrial anion carrier proteins located on the inner mitochondrial membrane, and their primary function is to leak protons from the intermembrane space into the mitochondrial matrix. The specific role of neuronal UCPs has been widely discussed and although there is no general agreement, there is a strong conviction that these proteins may be involved in the defense against mitochondrial reactive oxygen species (ROS) production and, consequently, protecting against oxidative damage. The generation of ROS is increasingly recognized as playing an important role in diabetes, neurodegenerative disorders and aging where mitochondria are both sources and targets of these reactive species. This review examines the neurodegenerative events associated with diabetes, highlighting the role of hyperglycemia and/or hypoglycemia on cognitive function. The role of mitochondria, neuronal UCPs and their impact in central nervous system will be elucidated. Finally, we will discuss neuronal UCPs as possible therapeutic targets for the treatment of diabetes-associated central complications and neurodegenerative diseases, namely Alzheimer's and Parkinson's diseases.
糖尿病是最常见的慢性疾病之一。由于葡萄糖是大脑的主要燃料，其水平应保持在狭窄范围内，以确保大脑功能正常。事实上，文献表明，无论是过高还是过低的血糖水平都会影响大脑结构和功能，从而导致认知障碍。解偶联蛋白（UCPs）是位于线粒体内膜上的一组线粒体阴离子载体蛋白，其主要功能是将质子从膜间腔泄漏到线粒体基质中。神经元 UCPs 的具体作用已被广泛讨论，尽管尚未达成普遍共识，但人们强烈认为这些蛋白质可能参与防御线粒体活性氧（ROS）的产生，并因此防止氧化损伤。ROS 的产生越来越被认为在糖尿病、神经退行性疾病和衰老中发挥重要作用，在这些疾病中，线粒体既是这些活性物质的来源也是其靶点。本综述探讨了与糖尿病相关的神经退行性事件，强调了高血糖和/或低血糖对认知功能的影响。将阐明线粒体、神经元 UCPs 及其对中枢神经系统的影响。最后，我们将讨论神经元 UCPs 作为治疗与糖尿病相关的中枢并发症和神经退行性疾病（如阿尔茨海默病和帕金森病）的潜在治疗靶点。
