Pastore Anna, Petrillo Sara, Piermarini Emanuela, Piemonte Fiorella
Unit of Muscular and Neurodegenerative Diseases, Children's Hospital and Research Institute IRCCS Bambino Gesù, Viale di San Paolo 15, 00146, Rome, Italy.
Curr Drug Metab. 2015;16(1):46-70. doi: 10.2174/138920021601150702161250.
Neurodegenerative diseases are characterized by a gradual and selective loss of neurons. ROS overload has been proved to occur early in this heterogeneous group of disorders, indicating oxidative stress as a primer factor underlying their pathogenesis. Given the importance of a better knowledge of the cause/effect of oxidative stress in the pathogenesis and evolution of neurodegeneration, recent efforts have been focused on the identification and determination of stable markers that may reflect systemic oxidative stress. This review provides an overview of these systemic redox biomarkers and their responsiveness to antioxidant therapies. Redox biomarkers can be classified as molecules that are modified by interactions with ROS in the microenvironment and antioxidant molecules that change in response to increased oxidative stress. DNA, lipids (including phospholipids), proteins and carbohydrates are examples of molecules that can be modified by excessive ROS in vivo. Some modifications have direct effects on molecule functions (e.g. to inhibit enzyme function), but others merely reflect the degree of oxidative stress in the local environment. Testing of redox biomarkers in neurodegenerative diseases has 3 important goals: 1) to confirm the presence or absence of systemic oxidative stress; 2) to identify possible underlying (and potentially reversible) causes of neurodegeneration; and 3) to estimate the severity of the disease and the risk of progression. Reflecting pathological processes occurring in the whole body, redox biomarkers may pinpoint novel therapeutic targets and lead to diagnose diseases before they are clinically evident.
神经退行性疾病的特征是神经元逐渐且选择性地丧失。活性氧（ROS）过载已被证明在这类异质性疾病的早期就会出现，这表明氧化应激是其发病机制的首要因素。鉴于更深入了解氧化应激在神经退行性变的发病机制和进展中的因果关系非常重要，最近的研究重点是识别和确定可能反映全身氧化应激的稳定标志物。本综述概述了这些全身氧化还原生物标志物及其对抗氧化疗法的反应性。氧化还原生物标志物可分为在微环境中与ROS相互作用而被修饰的分子以及因氧化应激增加而发生变化的抗氧化分子。DNA、脂质（包括磷脂）、蛋白质和碳水化合物是体内可被过量ROS修饰的分子的例子。一些修饰对分子功能有直接影响（例如抑制酶功能），但其他修饰仅反映局部环境中的氧化应激程度。在神经退行性疾病中检测氧化还原生物标志物有三个重要目标：1）确认全身氧化应激的存在与否；2）识别神经退行性变可能的潜在（且可能可逆）病因；3）评估疾病的严重程度和进展风险。氧化还原生物标志物反映了全身发生的病理过程，可能会确定新的治疗靶点，并在疾病临床显现之前实现疾病诊断。
