Facheris Maurizio, Beretta Simone, Ferrarese Carlo
Department of Neurosciences and Biomedical Technologies. University of Milano-Bicocca, Italy.
J Alzheimers Dis. 2004 Apr;6(2):177-84. doi: 10.3233/jad-2004-6210.
Oxidative stress has been implicated as a common pathogenetic mechanism in neurodegenerative disorders. Central nervous system is particularly exposed to free radical injury, given its high metal content, which can catalyze the formation of oxygen free radicals, and the relatively low content of antioxidant defenses. Indeed, several studies show markers of oxidative damage - lipid peroxidation, protein oxidation, DNA oxidation and glycoxidation markers - in brain areas affected by neurodegenerative disorders. Oxidative stress damage is intimately linked to glutamate neurotoxicity - known as "excitotoxicity". An excessive concentration of extracellular glutamate over-activates ionotropic glutamate receptors, resulting in intracellular calcium overload and a cascade of events leading to neural cell death. In this study we reviewed pathogenetic mechanisms that link oxidative stress and excitotoxicity in three neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease) and described peripheral markers of these mechanisms, that may be analyzed in patients as possible diagnostic and therapeutic tools.
氧化应激被认为是神经退行性疾病中一种常见的致病机制。鉴于中枢神经系统金属含量高，可催化氧自由基的形成，且抗氧化防御机制的含量相对较低，因此中枢神经系统特别容易受到自由基损伤。事实上，多项研究表明，在受神经退行性疾病影响的脑区中存在氧化损伤的标志物——脂质过氧化、蛋白质氧化、DNA氧化和糖氧化标志物。氧化应激损伤与谷氨酸神经毒性（即“兴奋性毒性”）密切相关。细胞外谷氨酸浓度过高会过度激活离子型谷氨酸受体，导致细胞内钙超载，并引发一系列导致神经细胞死亡的事件。在本研究中，我们回顾了三种神经退行性疾病（阿尔茨海默病、肌萎缩侧索硬化症和帕金森病）中氧化应激与兴奋性毒性之间的致病机制，并描述了这些机制的外周标志物，这些标志物可作为可能的诊断和治疗工具在患者中进行分析。
