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- Title
ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.
- Authors
Zhihui Zhong; Deane, Rashid; Ali, Zarina; Parisi, Margaret; Shapovalov, Yuriy; O'Banion, M. Kerry; Stojanovic, Konstantin; Sagare, Abhay; Boillee, Severine; Cleveland, Don W.; Zlokovic, Berislav V.
- 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.
- Subjects
MOTOR neuron diseases; AMYOTROPHIC lateral sclerosis; SUPEROXIDE dismutase; NEUROMUSCULAR diseases; SPINAL cord
- Publication
Nature Neuroscience, 2008, Vol 11, Issue 4, p420
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn2073