ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
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DOI：
10.1038/nn2073
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发表时间：
2008-04-01
影响因子：
25
通讯作者：
Zlokovic, Berislav V.
中科院分区：
文献类型：
--
作者：
Zhong, Zhihui;Deane, Rashid;Zlokovic, Berislav V.
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.
