Zhong Zhihui, Deane Rashid, Ali Zarina, Parisi Margaret, Shapovalov Yuriy, O'Banion M Kerry, Stojanovic Konstantin, Sagare Abhay, Boillee Severine, Cleveland Don W, Zlokovic Berislav V
Center for Neurodegenerative and Vascular Brain Disorders and Department of Neurosurgery, University of Rochester Medical Center, Kornberg Medical Research Bldg., 601 Elmwood Avenue, Box 670, Rochester, New York 14642, USA.
Nat Neurosci. 2008 Apr;11(4):420-2. doi: 10.1038/nn2073. Epub 2008 Mar 16.
We report here that amyotrophic lateral sclerosis-linked superoxide dismutase 1 (SOD1) mutants with different biochemical characteristics disrupted the blood-spinal cord barrier in mice by reducing the levels of the tight junction proteins ZO-1, occludin and claudin-5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation and hypoperfusion. SOD1 mutant-mediated endothelial damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, indicating that it was a central contributor to disease initiation.
我们在此报告，具有不同生化特性的肌萎缩侧索硬化症相关超氧化物歧化酶1（SOD1）突变体通过降低内皮细胞间紧密连接蛋白ZO-1、闭合蛋白和Claudin-5的水平，破坏了小鼠的血脊髓屏障。这导致了微出血，伴有神经毒性血红蛋白衍生产物的释放、微循环减少和灌注不足。SOD1突变体介导的内皮损伤在运动神经元变性和神经血管炎症反应发生之前就已累积，表明它是疾病起始的主要促成因素。
