ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
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- 16 March 2008
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 11 (4), 420-422
- https://doi.org/10.1038/nn2073
Abstract
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.Keywords
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