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

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.

SUBMITTER: Zhong Z

PROVIDER: S-EPMC2895310 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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

Zhong Zhihui Z Deane Rashid R Ali Zarina Z Parisi Margaret M Shapovalov Yuriy Y O'Banion M Kerry MK Stojanovic Konstantin K Sagare Abhay A Boillee Severine S Cleveland Don W DW Zlokovic Berislav V BV

Nature neuroscience 20080316 4

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 ...[more]

PMID: 18344992

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