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Nat Neurosci. 2008 Apr;11(4):420-2. doi: 10.1038/nn2073. Epub 2008 Mar 16.

ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.

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1
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.

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.

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PMID:
18344992
PMCID:
PMC2895310
DOI:
10.1038/nn2073
[Indexed for MEDLINE]
Free PMC Article

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