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- Title
The role of the oxidative stress metabolism in the central nervous system at the pre-symptomatic and symptomatic stages of the ALS disease.
- Authors
Aydemir, Duygu; Kulaç, İbrahim; Başak, Ayşe Nazlı; Ulusu, Nuriye Nuray
- Abstract
Objective: ALS is the most common motor neuron disease. Despite incidence of the disease is increasing, there is no effective treatment against ALS and urgent therapeutic approaches are required for the treatment of people with ALS. Thus, we investigated oxidative stress metabolism and antioxidant capacity of the central nervous system at the pre-symptomatic and symptomatic stages of ALS. Methods: SOD1G93A mutated albino male rats (n=90) were used for the experiments. Mitochondrial and cytosolic fractions of the brain and spinal cord were prepared and used for the experiments. H&E, OLIG2 and myelin staining were performed to evaluate histopathological experiments. Glucose-6 phosphate dehydrogenase (G6PD), 6-phosphoglucanate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione-s transferase (GST), catalase (CAT), superoxide dismutase 1 (SOD1), isocitrate dehydrogenase 1,2,3 (IDH1,2,3) were evaluated in brain and spinal cord. Human mutant SOD1G93A protein aggregation was evaluated via western blot, where enzyme activity and ELISA was performed via spectrophotometer. Results: Cytosolic and mitochondrial G6PD, 6-PGD, GR, GST, CAT, SOD1, IDH1, IDH2 and IDH3 enzyme activities were impaired in the SOD1G93A mutated rats compared to the wild type rats of each group in both spinal cord and brain. OLIG2 expression increased in the ALS rats, where histopathological alterations were observed in the SOD1G93A rats. Additionally, SOD1G93A protein aggregation were observed in the cytosol and mitochondria of both spinal cord and brain. Conclusion: Oxidative stress metabolism and pentose phosphate pathway (PPP) have been impaired because of the accumulation of human mutant SOD1G93A protein accumulation. Impaired oxidative stress metabolism results in the histopathological changes in the spinal cord and brain tissues of ALS rats. Therefore, targeting oxidative stress metabolism and PPP can be a promising therapeutic target to cure people with ALS in the future.
- Subjects
CENTRAL nervous system; OXIDATIVE stress; MOTOR neuron diseases; AMYOTROPHIC lateral sclerosis; PENTOSE phosphate pathway; SPINAL cord; MUTANT proteins
- Publication
Anatomy: International Journal of Experimental & Clinical Anatomy, 2022, Vol 16, p220
- ISSN
1307-8798
- Publication type
Abstract
- DOI
10.2399/ana.22.003s