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Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation

Overview of attention for article published in Brain: A Journal of Neurology, April 2012
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  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

Mentioned by

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1 tweeter
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1 patent

Readers on

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98 Mendeley
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2 CiteULike
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Title
Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation
Published in
Brain: A Journal of Neurology, April 2012
DOI 10.1093/brain/aws100
Pubmed ID
Authors

Steven Petratos, Ezgi Ozturk, Michael F. Azari, Rachel Kenny, Jae Young Lee, Kylie A. Magee, Alan R. Harvey, Courtney McDonald, Kasra Taghian, Leon Moussa, Pei Mun Aui, Christopher Siatskas, Sara Litwak, Michael G. Fehlings, Stephen M. Strittmatter, Claude C. A. Bernard

Abstract

Multiple sclerosis involves demyelination and axonal degeneration of the central nervous system. The molecular mechanisms of axonal degeneration are relatively unexplored in both multiple sclerosis and its mouse model, experimental autoimmune encephalomyelitis. We previously reported that targeting the axonal growth inhibitor, Nogo-A, may protect against neurodegeneration in experimental autoimmune encephalomyelitis; however, the mechanism by which this occurs is unclear. We now show that the collapsin response mediator protein 2 (CRMP-2), an important tubulin-associated protein that regulates axonal growth, is phosphorylated and hence inhibited during the progression of experimental autoimmune encephalomyelitis in degenerating axons. The phosphorylated form of CRMP-2 (pThr555CRMP-2) is localized to spinal cord neurons and axons in chronic-active multiple sclerosis lesions. Specifically, pThr555CRMP-2 is implicated to be Nogo-66 receptor 1 (NgR1)-dependent, since myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced NgR1 knock-out (ngr1(-)(/)(-)) mice display a reduced experimental autoimmune encephalomyelitis disease progression, without a deregulation of ngr1(-)(/)(-) MOG(35-55)-reactive lymphocytes and monocytes. The limitation of axonal degeneration/loss in experimental autoimmune encephalomyelitis-induced ngr1(-)(/)(-) mice is associated with lower levels of pThr555CRMP-2 in the spinal cord and optic nerve during experimental autoimmune encephalomyelitis. Furthermore, transduction of retinal ganglion cells with an adeno-associated viral vector encoding a site-specific mutant T555ACRMP-2 construct, limits optic nerve axonal degeneration occurring at peak stage of experimental autoimmune encephalomyelitis. Therapeutic administration of the anti-Nogo(623-640) antibody during the course of experimental autoimmune encephalomyelitis, associated with an improved clinical outcome, is demonstrated to abrogate the protein levels of pThr555CRMP-2 in the spinal cord and improve pathological outcome. We conclude that phosphorylation of CRMP-2 may be downstream of NgR1 activation and play a role in axonal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Blockade of Nogo-A/NgR1 interaction may serve as a viable therapeutic target in multiple sclerosis.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 98 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 1%
Netherlands 1 1%
Iran, Islamic Republic of 1 1%
Spain 1 1%
United States 1 1%
Unknown 93 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 26 27%
Researcher 16 16%
Student > Master 11 11%
Student > Bachelor 10 10%
Student > Doctoral Student 8 8%
Other 17 17%
Unknown 10 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 33 34%
Medicine and Dentistry 20 20%
Neuroscience 14 14%
Biochemistry, Genetics and Molecular Biology 5 5%
Engineering 2 2%
Other 8 8%
Unknown 16 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 May 2018.
All research outputs
#3,689,400
of 12,974,522 outputs
Outputs from Brain: A Journal of Neurology
#2,706
of 5,011 outputs
Outputs of similar age
#32,826
of 119,743 outputs
Outputs of similar age from Brain: A Journal of Neurology
#31
of 68 outputs
Altmetric has tracked 12,974,522 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 5,011 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.6. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 119,743 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.