Tetramethylpyrazine nitrone improves motor dysfunction and pathological manifestations by activating the PGC-1α/Nrf2/HO-1 pathway in ALS mice
| Autor: | Baojian Guo, Shupeng Li, Jie Cao, Chengyou Zheng, Zaijun Zhang, Jing Wen, Pei Yu, Liangmiao Wu, Yangwen Luo, Gaoxiao Zhang, Fengjiao Wang, Xifei Yang, Shangming Li, Yuqiang Wang, Yewei Sun |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty NF-E2-Related Factor 2 SOD1 Mice Transgenic medicine.disease_cause Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Superoxide Dismutase-1 Internal medicine Medicine Tetramethylpyrazine Animals Humans Amyotrophic lateral sclerosis Muscle Skeletal Pharmacology Denervation Hand Strength business.industry Amyotrophic Lateral Sclerosis Skeletal muscle Membrane Proteins Motor neuron medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Pyrazines Female business 030217 neurology & neurosurgery Oxidative stress Heme Oxygenase-1 |
| Zdroj: | Neuropharmacology. 182 |
| ISSN: | 1873-7064 |
| Popis: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy, weakness and paralysis. Oxidative stress plays a key role in the pathogenesis of ALS, including familial forms of the disease arising from mutation of the gene coding for superoxide dismutase (SOD1). We have used the SOD1G93A ALS mouse model to investigate the efficacy of 2-[[(1,1-dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a novel tetramethylpyrazine derivative armed with a powerful free-radical scavenging nitrone moiety. TBN was administered to mice by intraperitoneal or intragastric injection after the onset of motor deficits. TBN slowed the progression of motor neuron disease as evidenced by improved motor performance, reduced spinal motor neuron loss and the associated glial response, and decreased skeletal muscle fiber denervation and fibrosis. TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1. These findings suggest that TBN holds promise as a therapeutic agent for ALS. |
| Databáze: | OpenAIRE |
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