The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
Open accessAbstract
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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“Studies in SOD1 transgenic mice expressing dismutase-active (G93A and G37R) and dismutase-inactive (G85R) mutations have suggested that BSCB breakdown occurs before motor neuron injury (194, 415, 651, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
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“BBB disruption including diminished levels of TJ proteins, immunoglobulin G (IgG) and hemosiderin perivascular deposits, and GLUT1 reduction has been shown to precede neuroinflammation, motor neuron loss, and motor impairment in different types of SOD1 mutants (415, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
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“For instance, SOD1 G93A mice develop ultrastructural capillary alterations, extravasation of RBCs, and deposition of fibrin(ogen) and hemosiderin deposits in the brain stem and spinal cord early in the disease (194, 651, 687).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
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Citations
Cites
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623
Self-citationALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Velde, C. V., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,476
Self-citationOosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Dorpe, J. V., Hellings, P., Gorselink, M., Heymans, S., et al. (2001) · Nature Genetics · doi:10.1038/88842 · Cited by 1,007
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Neurovascular mechanisms of Alzheimer's neurodegeneration
Zlokovic, B. V. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.02.001 · Cited by 770
Pun, S., Santos, A. F., Saxena, S., Xu, L., & Caroni, P. (2006) · Nature Neuroscience · doi:10.1038/nn1653 · Cited by 689
Axonal damage markers in cerebrospinal fluid are increased in ALS
Brettschneider, J., Petzold, A., Süßmuth, S. D., Ludolph, A. C., & Tumani, H. (2006) · Neurology · doi:10.1212/01.wnl.0000203120.85850.54 · Cited by 261
Garbuzova-Davis, S. N., Saporta, S., Haller, E. M., Kolomey, I., Bennett, S. P., Potter, H., & Sanberg, P. R. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001205 · Cited by 253
Ultrastructure of blood–brain barrier and blood–spinal cord barrier in SOD1 mice modeling ALS
Garbuzova-Davis, S., Haller, E., Saporta, S., Kolomey, I., Nicosia, S. V., & Sanberg, P. R. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.044 · Cited by 239
Pasinelli, P., Borchelt, D., Houseweart, M. K., Cleveland, D. W., & Brown, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15763 · Cited by 221
Self-citationMicroglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis
Sargsyan, S. A., Monk, P. N., & Shaw, P. J. (2005) · Glia · doi:10.1002/glia.20210 · Cited by 207
Lobsiger, C. S., Boillée, S., & Cleveland, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702230104 · Cited by 139
Self-citationKamei, Y., Inagaki, N., Nishizawa, M., Tsutsumi, O., Taketani, Y., & Inagaki, M. (1998) · Glia · doi:10.1002/(sici)1098-1136(199807)23:3 · Cited by 114
Toxic Effect of Hemoglobin on Spinal Cord Neurons in Culture
Regan, R. F., & Guo, Y. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.645 · Cited by 69
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Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Self-citationNeurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452
Metadata
- Authors
- Zhong, Z., Deane, R., Ali, Z., Parisi, M., Shapovalov, Y., O'Banion, M. K., Stojanovic, K., Sagare, A., Boillee, S., Cleveland, D. W., & Zlokovic, B. V.
- Affiliations
- University of Rochester Medicine (US)
- Ludwig Cancer Research (BE)
- Venue
- Nature Neuroscience
- Published
- 2008-03-16
- Volume
- 11
- Issue
- 4
- Pages
- 420-422
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2895310
- OpenAlex
- W1968758728
- Cited by
- 476
- References
- 15
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 29 · 2023: 26 · 2022: 20 · 2021: 33 · 2020: 27 · 2019: 26 · 2018: 22 · 2017: 18 · 2016: 18 · 2015: 25 · 2014: 32 · 2013: 28 · 2012: 31
- FWCI
- 23.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R37AG023084)
- National Heart, Lung, and Blood Institute (HL63290, R01HL063290)
- National Institute of Neurological Disorders and Stroke (R37NS034467, R37 NS 27036, R37NS027036, R01NS034467, R37NS34467)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Keywords
- amyotrophic lateral sclerosis, mutant SOD1, blood-spinal cord barrier, tight junction proteins, ZO-1, occludin, claudin-5, endothelial injury, microhemorrhages, microcirculation, hypoperfusion, neurovascular inflammation, motor neuron degeneration, disease initiation
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Blood-Brain Barrier, Capillaries, Endothelium, Vascular, Hemorrhage, Humans, Isoenzymes, Membrane Proteins, Mice, Mutant Strains, Motor Neurons, Nerve Degeneration, Phosphoproteins, Spinal Cord, Superoxide Dismutase, Disease Progression, Tight Junctions, Mice, Claudin-5, Occludin, Zonula Occludens-1 Protein
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