后肢运动神经元需要铜锌超氧化物歧化酶来维持神经肌肉接头。
Hindlimb motor neurons require Cu/Zn superoxide dismutase for maintenance of neuromuscular junctions.
作者信息
Flood D G, Reaume A G, Gruner J A, Hoffman E K, Hirsch J D, Lin Y G, Dorfman K S, Scott R W
机构信息
Department of Molecular Biology, Cephalon, Inc., West Chester, Pennsylvania, USA.
出版信息
Am J Pathol. 1999 Aug;155(2):663-72. doi: 10.1016/S0002-9440(10)65162-0.
Abstract
The role of oxidative damage in neurodegenerative disease was investigated in mice lacking cytoplasmic Cu/Zn superoxide dismutase (SOD), created by deletion of the SOD1 gene (SOD1(-/-)). SOD1(-/-) mice developed a chronic peripheral hindlimb axonopathy. Mild denervation of muscle was detected at 2 months, and behavioral and physiological motor deficits were present at 5-7 months of age. Ventral root axons were shrunken but were normal in number. The somatosensory system in SOD1(-/-) mice was mildly affected. SOD1(-/-) mice expressing Cu/Zn SOD only in brain and spinal cord were generated using transgenic mice expressing mouse SOD1 driven by the neuron-specific synapsin promoter. Neuron-specific expression of Cu/Zn SOD in SOD1(-/-) mice rescued motor neurons from the neuropathy. Therefore, Cu/Zn SOD is not required for normal motor neuron survival, but is necessary for the maintenance of normal neuromuscular junctions by hindlimb motor neurons.
摘要
通过缺失SOD1基因（SOD1(-/-)）构建缺乏细胞质铜锌超氧化物歧化酶（SOD）的小鼠，研究氧化损伤在神经退行性疾病中的作用。SOD1(-/-)小鼠出现慢性外周后肢轴索性神经病。2个月时检测到轻度肌肉去神经支配，5至7个月大时出现行为和生理运动缺陷。腹根轴突萎缩但数量正常。SOD1(-/-)小鼠的体感系统受到轻度影响。使用由神经元特异性突触素启动子驱动表达小鼠SOD1的转基因小鼠，培育出仅在脑和脊髓中表达铜锌SOD的SOD1(-/-)小鼠。SOD1(-/-)小鼠中铜锌SOD的神经元特异性表达使运动神经元免受神经病变影响。因此，正常运动神经元存活不需要铜锌SOD，但后肢运动神经元维持正常神经肌肉接头需要铜锌SOD。
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本文引用的文献
1
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Science. 1998 Sep 18;281(5384):1851-4. doi: 10.1126/science.281.5384.1851.
2
Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn superoxide dismutase mutants and H2O2.对家族性肌萎缩侧索硬化症相关的铜锌超氧化物歧化酶突变体与过氧化氢反应形成羟基自由基加合物的机制的重新审视。
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6675-80. doi: 10.1073/pnas.95.12.6675.
3
Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant.在整个肌萎缩侧索硬化症（ALS）样疾病中，游离硝基酪氨酸水平升高，但蛋白质结合的硝基酪氨酸或羟基自由基水平未升高，这表明酪氨酸硝化是一种家族性ALS相关超氧化物歧化酶1突变体在体内的异常特性。
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7606-11. doi: 10.1073/pnas.94.14.7606.
4
Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia.铜锌超氧化物歧化酶活性降低会加重短暂性局灶性脑缺血后的神经元细胞损伤和水肿形成。
J Neurosci. 1997 Jun 1;17(11):4180-9. doi: 10.1523/JNEUROSCI.17-11-04180.1997.
5
ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions.与肌萎缩侧索硬化症相关的超氧化物歧化酶1（SOD1）突变体G85R介导对星形胶质细胞的损伤，并通过含SOD1的包涵体促进疾病快速进展。
Neuron. 1997 Feb;18(2):327-38. doi: 10.1016/s0896-6273(00)80272-x.
6
7
Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9782-7. doi: 10.1073/pnas.93.18.9782.
8
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9
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10
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