| Title |
Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa
|
|---|---|
| Published in |
Molecular Neurodegeneration, April 2018
|
| DOI | 10.1186/s13024-018-0251-y |
| Pubmed ID | |
| Authors |
Alonso Sánchez-Cruz, Beatriz Villarejo-Zori, Miguel Marchena, Josefa Zaldivar-Díez, Valle Palomo, Carmen Gil, Ignacio Lizasoain, Pedro de la Villa, Ana Martínez, Enrique J. de la Rosa, Catalina Hernández-Sánchez |
| Abstract |
Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death of photoreceptor cells, resulting in visual loss and, eventually, blindness. To date, no effective therapies have been transferred to clinic. Given the diverse genetic etiology of RP, targeting common cellular and molecular retinal alterations has emerged as a potential therapeutic strategy. Using the Pde6b rd10/rd10 mouse model of RP, we investigated the effects of daily intraperitoneal administration of VP3.15, a small-molecule heterocyclic GSK-3 inhibitor. Gene expression was analyzed by quantitative PCR and protein expression and phosphorylation by Western blot. Photoreceptor preservation was evaluated by histological analysis and visual function was assessed by electroretinography. In rd10 retinas, increased expression of pro-inflammatory markers and reactive gliosis coincided with the early stages of retinal degeneration. Compared with wild-type controls, GSK-3β expression (mRNA and protein) remained unchanged during the retinal degeneration period. However, levels of GSK-3βSer9 and its regulator AktSer473 were increased in rd10 versus wild-type retinas. In vivo administration of VP3.15 reduced photoreceptor cell loss and preserved visual function. This neuroprotective effect was accompanied by a decrease in the expression of neuroinflammatory markers. These results provide proof of concept of the therapeutic potential of VP3.15 for the treatment of retinal neurodegenerative conditions in general, and RP in particular. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 7 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 86% |
| Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 21% |
| Student > Master | 6 | 16% |
| Student > Bachelor | 3 | 8% |
| Researcher | 3 | 8% |
| Student > Doctoral Student | 2 | 5% |
| Other | 6 | 16% |
| Unknown | 10 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 24% |
| Neuroscience | 7 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Immunology and Microbiology | 2 | 5% |
| Medicine and Dentistry | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 10 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 26 June 2020.
All research outputs
#4,699,673
of 23,043,346 outputs
Outputs from Molecular Neurodegeneration
#536
of 857 outputs
Outputs of similar age
#83,434
of 296,868 outputs
Outputs of similar age from Molecular Neurodegeneration
#14
of 17 outputs
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