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Role of the sigma-1 receptor chaperone in rod and cone photoreceptor degenerations in a mouse model of retinitis pigmentosa

Overview of attention for article published in Molecular Neurodegeneration, September 2017
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Title
Role of the sigma-1 receptor chaperone in rod and cone photoreceptor degenerations in a mouse model of retinitis pigmentosa
Published in
Molecular Neurodegeneration, September 2017
DOI 10.1186/s13024-017-0202-z
Pubmed ID
Authors

Huan Yang, Yingmei Fu, Xinying Liu, Pawan K. Shahi, Timur A. Mavlyutov, Jun Li, Annie Yao, Steven Z.-W. Guo, Bikash R. Pattnaik, Lian-Wang Guo

Abstract

Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones. The mechanisms underlying the S1R protection for cones are not understood in detail. By rearing rd10/S1R(-/-) and rd10/S1R(+/+) mice in dim light to decelerate rapid rod/cone degeneration, we were able to compare their retinal biochemistry, histology and functions throughout postnatal 3-6 weeks (3 W-6 W). The receptor-interacting protein kinases (RIP1/RIP3) and their interaction (proximity ligation) dramatically up-regulated after 5 W in rd10/S1R(-/-) (versus rd10/S1R(+/+)) retinas, indicative of intensified necroptosis activation, which was accompanied by exacerbated loss of cones. Greater rod loss in rd10/S1R(-/-) versus rd10/S1R(+/+) retinas was evidenced by more cleaved Caspase3 (4 W) and lower rod electro-retinographic a-waves (4 W-6 W), concomitant with reduced LC3-II and CHOP (4 W-6 W), markers of autophagy and endoplasmic reticulum stress response, respectively. However, the opposite occurred at 3 W. This study reveals previously uncharacterized S1R-associated mechanisms during rd10 photoreceptor degeneration, including S1R's influences on necroptosis and autophagy as well as its biphasic role in rod degeneration upstream of cone death.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 22%
Student > Ph. D. Student 3 13%
Student > Postgraduate 2 9%
Student > Bachelor 2 9%
Professor > Associate Professor 2 9%
Other 5 22%
Unknown 4 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 26%
Medicine and Dentistry 5 22%
Neuroscience 3 13%
Biochemistry, Genetics and Molecular Biology 2 9%
Nursing and Health Professions 1 4%
Other 1 4%
Unknown 5 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 21 September 2017.
All research outputs
#9,063,438
of 11,805,285 outputs
Outputs from Molecular Neurodegeneration
#429
of 515 outputs
Outputs of similar age
#179,418
of 267,737 outputs
Outputs of similar age from Molecular Neurodegeneration
#21
of 23 outputs
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So far Altmetric has tracked 515 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
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We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.