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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...

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Autores principales: Eitan, Erez, Tichon, Ailon, Gazit, Aviv, Gitler, Daniel, Slavin, Shimon, Priel, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2012
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.
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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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