Department of Biomedical and Specialist Surgical Sciences, Section of Neurological, Psychiatric and Psychological Sciences, University of Ferrara, Ferrara, Italy.
Interdepartmental Research Center for the Study of Multiple Sclerosis and Inflammatory and Degenerative Diseases of the Nervous System, University of Ferrara, Ferrara, Italy.
J Neuroinflammation. 2019 Jun 27;16(1):131. doi: 10.1186/s12974-019-1526-0.
An alteration of autophagy and mitophagy, two highly conserved lysosome-dependent degradation pathways involved in the maintenance of cellular homeostasis, has been associated with multiple sclerosis (MS).
To search the level of autophagy-related 5 (ATG5) and Parkin proteins, as markers of autophagy and mitophagy respectively, and lactate in a cohort of MS patients.
Cerebrospinal fluid (CSF) and serum samples from 60 MS patients were analyzed: 30 with magnetic resonance imaging (MRI) evidence of disease activity, gadolinium (Gd)-based contrast agent positive (Gd+), and 30 without MRI evidence of disease activity (Gd-). ATG5, Parkin, and lactate were measured using commercially available products.
Serum levels of ATG5, Parkin, and lactate were more elevated in Gd+ than in Gd- MS patients (p < 0.0001), and CSF concentrations of ATG5 and Parkin were greater in Gd+ than in Gd- MS (p < 0.0001). Our results demonstrated that molecular markers of autophagy and mitophagy are increased in CSF of MS patients during the active phases of the disease and that these catabolic markers, together with lactate, are also remarkably augmented in blood suggesting a role of these processes in MS pathogenesis and the possible use of these molecules as biomarkers of disease activity.
自噬和线粒体自噬的改变，这两种高度保守的溶酶体依赖性降解途径与细胞内稳态的维持有关，与多发性硬化症（MS）有关。
在一组 MS 患者中寻找自噬相关蛋白 5（ATG5）和 Parkin 蛋白（分别作为自噬和线粒体自噬的标志物）和乳酸的水平。
分析了 60 名 MS 患者的脑脊液（CSF）和血清样本：30 名具有疾病活动的磁共振成像（MRI）证据，钆（Gd）基造影剂阳性（Gd+），30 名无 MRI 疾病活动证据（Gd-）。使用市售产品测量 ATG5、Parkin 和乳酸。
Gd+MS 患者的血清 ATG5、Parkin 和乳酸水平明显高于 Gd-MS 患者（p<0.0001），Gd+MS 患者的 CSF 中 ATG5 和 Parkin 浓度高于 Gd-MS 患者（p<0.0001）。我们的结果表明，在疾病活动期，MS 患者的 CSF 中自噬和线粒体自噬的分子标志物增加，并且这些代谢标志物与乳酸一起在血液中显著增加，提示这些过程在 MS 发病机制中的作用以及这些分子作为疾病活动生物标志物的可能用途。
