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Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

作者:Lidia, De Riccardis;Alessandra, Ferramosca;Antonio, Danieli;Giorgio, Trianni;Vincenzo, Zara;Francesca, De Robertis;Michele, Maffia

来源:BBA clinical 2016 年 6卷

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作者:
Lidia, De Riccardis;Alessandra, Ferramosca;Antonio, Danieli;Giorgio, Trianni;Vincenzo, Zara;Francesca, De Robertis;Michele, Maffia
来源:
BBA clinical 2016 年 6卷
标签:
CAT, catalase CD4+ T cells CNS, central nervous system CS, citrate synthase EAE, experimental autoimmune encephalomyelitis GPX, glutathione peroxidase GR, glutathione reductase Glycolysis HK, hexokinase MCT, mono-carboxylate transporters MS, Multiple Sclerosis Multiple sclerosis OXPHOS OXPHOS, oxidative phosphorylation Oxidative stress PBMC, peripheral blood mononuclear cell PFK, phosphofructokinase RCR, respiratory control ratio ROS, reactive oxygen species RRMS, Relapsing-Remitting Multiple Sclerosis SOD, superoxide dismutase Th, T helper
Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.