BACKGROUND: Pathophysiological mechanisms that contribute to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) include oxidative stress and inflammation. We conducted a preliminary study to explore these mechanisms, to discuss their link in ALS, and to determine the feasibility of incorporating this combined analysis into current biomarkers research. METHODS: We enrolled 10 ALS patients and 10 controls. We measured the activities of glutathione peroxidase, glutathione reductase, superoxyde dismutase (SOD), and the levels of serum total antioxidant status (TAS), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and glutathione status (e.g. glutathione disulfide, GSSG/reduced glutathione, GSH). We analysed the concentrations of homocysteine, several cytokines, vitamins and metals by standard methods used in routine practice. RESULTS: There was a significant decrease in TAS levels (p=0.027) and increase in 8-OHdG (p=0.014) and MDA (p=0.011) levels in ALS patients. We also observed a significantly higher GSSG/GSH ratio (p=0.022), and IL-6 (p=0.0079) and IL-8 (p=0.009) concentrations in ALS patients. Correlations were found between biological and clinical markers (homosysteine vs. clinical status at diagnosis, p=0.02) and between some biological markers such as IL-6 vs. GSSG/GSH (p=0.045) or SOD activity (p=0.017). CONCLUSION: We confirmed the systemic alteration of both the redox and the inflammation status in ALS patients, and we observed a link with some clinical parameters. These promising results encourage us to pursue this study with collection of combined oxidative stress and inflammatory markers.
BACKGROUND: Pathophysiological mechanisms that contribute to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) include oxidative stress and inflammation. We conducted a preliminary study to explore these mechanisms, to discuss their link in ALS, and to determine the feasibility of incorporating this combined analysis into current biomarkers research. METHODS: We enrolled 10 ALSpatients and 10 controls. We measured the activities of glutathione peroxidase, glutathione reductase, superoxyde dismutase (SOD), and the levels of serum total antioxidant status (TAS), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and glutathione status (e.g. glutathione disulfide, GSSG/reduced glutathione, GSH). We analysed the concentrations of homocysteine, several cytokines, vitamins and metals by standard methods used in routine practice. RESULTS: There was a significant decrease in TAS levels (p=0.027) and increase in 8-OHdG (p=0.014) and MDA (p=0.011) levels in ALSpatients. We also observed a significantly higher GSSG/GSH ratio (p=0.022), and IL-6 (p=0.0079) and IL-8 (p=0.009) concentrations in ALSpatients. Correlations were found between biological and clinical markers (homosysteine vs. clinical status at diagnosis, p=0.02) and between some biological markers such as IL-6 vs. GSSG/GSH (p=0.045) or SOD activity (p=0.017). CONCLUSION: We confirmed the systemic alteration of both the redox and the inflammation status in ALSpatients, and we observed a link with some clinical parameters. These promising results encourage us to pursue this study with collection of combined oxidative stress and inflammatory markers.
Authors: Hiroshi Mitsumoto; Diana C Garofalo; Regina M Santella; Eric J Sorenson; Björn Oskarsson; J Americo M Fernandes; Howard Andrews; Jonathan Hupf; Madison Gilmore; Daragh Heitzman; Richard S Bedlack; Jonathan S Katz; Richard J Barohn; Edward J Kasarskis; Catherine Lomen-Hoerth; Tahseen Mozaffar; Sharon P Nations; Andrea J Swenson; Pam Factor-Litvak Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2020-04-10 Impact factor: 4.092
Authors: I Vazquez-Villaseñor; C J Garwood; P R Heath; J E Simpson; P G Ince; S B Wharton Journal: Neuropathol Appl Neurobiol Date: 2019-06-17 Impact factor: 8.090
Authors: Margarita Gerou; Benjamin Hall; Ryan Woof; Jessica Allsop; Stephen J Kolb; Kathrin Meyer; Pamela J Shaw; Scott P Allen Journal: Neurobiol Aging Date: 2021-04-27 Impact factor: 4.673