Sheffield Institute for Translational Neurosciences, University of Sheffield, Sheffield S10 2HQ, UK.
Int J Mol Sci. 2020 Nov 24;21(23):8924. doi: 10.3390/ijms21238924.
Neurodegenerative diseases are a group of nervous system conditions characterised pathologically by the abnormal deposition of protein throughout the brain and spinal cord. One common pathophysiological change seen in all neurodegenerative disease is a change to the metabolic function of nervous system and peripheral cells. Glycolysis is the conversion of glucose to pyruvate or lactate which results in the generation of ATP and has been shown to be abnormal in peripheral cells in Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Changes to the glycolytic pathway are seen early in neurodegenerative disease and highlight how in multiple neurodegenerative conditions pathology is not always confined to the nervous system. In this paper, we review the abnormalities described in glycolysis in the three most common neurodegenerative diseases. We show that in all three diseases glycolytic changes are seen in fibroblasts, and red blood cells, and that liver, kidney, muscle and white blood cells have abnormal glycolysis in certain diseases. We highlight there is potential for peripheral glycolysis to be developed into multiple types of disease biomarker, but large-scale bio sampling and deciphering how glycolysis is inherently altered in neurodegenerative disease in multiple patients' needs to be accomplished first to meet this aim.
神经退行性疾病是一组神经系统疾病,其病理特征是蛋白质在大脑和脊髓中的异常沉积。所有神经退行性疾病中常见的一种共同的病理生理变化是神经系统和外周细胞代谢功能的改变。糖酵解是葡萄糖转化为丙酮酸或乳酸,导致 ATP 的产生,并且已经在阿尔茨海默病、帕金森病和肌萎缩侧索硬化症的外周细胞中显示出异常。糖酵解途径的改变在神经退行性疾病的早期就出现了,这突出表明在多种神经退行性疾病中,病理并不总是局限于神经系统。在本文中,我们综述了三种最常见的神经退行性疾病中描述的糖酵解异常。我们表明,在所有三种疾病中,成纤维细胞和红细胞中都存在糖酵解变化,并且在某些疾病中,肝脏、肾脏、肌肉和白细胞的糖酵解也存在异常。我们强调,外周糖酵解有可能发展成为多种疾病生物标志物,但首先需要完成大规模的生物样本采集,并阐明在多个患者的神经退行性疾病中糖酵解是如何固有改变的,以实现这一目标。
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