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Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis
Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
WILEY-VCH Verlag
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376858/ https://www.ncbi.nlm.nih.gov/pubmed/22351600 http://dx.doi.org/10.1002/emmm.201200212 |
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author | Eitan, Erez Tichon, Ailon Gazit, Aviv Gitler, Daniel Slavin, Shimon Priel, Esther |
author_facet | Eitan, Erez Tichon, Ailon Gazit, Aviv Gitler, Daniel Slavin, Shimon Priel, Esther |
author_sort | Eitan, Erez |
collection | PubMed |
description | Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents. In this study, we demonstrate for the first time that the novel compound AGS-499 increases telomerase activity and expression in the mouse brain and spinal cord (SC). It exerts neuroprotective effects in NMDA-injected CD-1 mice, delays the onset and progression of the amyotrophic lateral sclerosis (ALS) disease in SOD1 transgenic mice, and, after the onset of ALS, it increases the survival of motor neurons in the SC by 60%. The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated. Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects. |
format | Online Article Text |
id | pubmed-3376858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-33768582012-09-17 Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis Eitan, Erez Tichon, Ailon Gazit, Aviv Gitler, Daniel Slavin, Shimon Priel, Esther EMBO Mol Med Research Article Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents. In this study, we demonstrate for the first time that the novel compound AGS-499 increases telomerase activity and expression in the mouse brain and spinal cord (SC). It exerts neuroprotective effects in NMDA-injected CD-1 mice, delays the onset and progression of the amyotrophic lateral sclerosis (ALS) disease in SOD1 transgenic mice, and, after the onset of ALS, it increases the survival of motor neurons in the SC by 60%. The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated. Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects. WILEY-VCH Verlag 2012-04 /pmc/articles/PMC3376858/ /pubmed/22351600 http://dx.doi.org/10.1002/emmm.201200212 Text en Copyright © 2012 EMBO Molecular Medicine |
spellingShingle | Research Article Eitan, Erez Tichon, Ailon Gazit, Aviv Gitler, Daniel Slavin, Shimon Priel, Esther Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title | Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title_full | Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title_fullStr | Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title_full_unstemmed | Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title_short | Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
title_sort | novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376858/ https://www.ncbi.nlm.nih.gov/pubmed/22351600 http://dx.doi.org/10.1002/emmm.201200212 |
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