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Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer’s disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impai...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297816/ https://www.ncbi.nlm.nih.gov/pubmed/28106772 http://dx.doi.org/10.3390/ijms18010184 |
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author | Porrini, Vanessa Sarnico, Ilenia Benarese, Marina Branca, Caterina Mota, Mariana Lanzillotta, Annamaria Bellucci, Arianna Parrella, Edoardo Faggi, Lara Spano, Pierfranco Imbimbo, Bruno Pietro Pizzi, Marina |
author_facet | Porrini, Vanessa Sarnico, Ilenia Benarese, Marina Branca, Caterina Mota, Mariana Lanzillotta, Annamaria Bellucci, Arianna Parrella, Edoardo Faggi, Lara Spano, Pierfranco Imbimbo, Bruno Pietro Pizzi, Marina |
author_sort | Porrini, Vanessa |
collection | PubMed |
description | CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer’s disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis. We here tested the possible anti-apoptotic and neuroprotective activity of CSP-1103 in a cell-based model of post-ischemic injury, wherein the primary mouse cortical neurons were exposed to oxygen-glucose deprivation (OGD). When added after OGD, CSP-1103 prevented the apoptosis cascade by reducing cytochrome c release and caspase-3 activation and the secondary necrosis. Additionally, CSP-1103 limited earlier activation of p38 and nuclear factor κB (NF-κB) pathways. These results demonstrate that CSP-1103 is neuroprotective in a model of post-ischemic brain injury and provide further mechanistic insights as regards its ability to reduce apoptosis and potential production of pro-inflammatory cytokines. In conclusion, these findings suggest a potential use of CSP-1103 for the treatment of brain ischemia. |
format | Online Article Text |
id | pubmed-5297816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-52978162017-02-10 Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation Porrini, Vanessa Sarnico, Ilenia Benarese, Marina Branca, Caterina Mota, Mariana Lanzillotta, Annamaria Bellucci, Arianna Parrella, Edoardo Faggi, Lara Spano, Pierfranco Imbimbo, Bruno Pietro Pizzi, Marina Int J Mol Sci Article CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer’s disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis. We here tested the possible anti-apoptotic and neuroprotective activity of CSP-1103 in a cell-based model of post-ischemic injury, wherein the primary mouse cortical neurons were exposed to oxygen-glucose deprivation (OGD). When added after OGD, CSP-1103 prevented the apoptosis cascade by reducing cytochrome c release and caspase-3 activation and the secondary necrosis. Additionally, CSP-1103 limited earlier activation of p38 and nuclear factor κB (NF-κB) pathways. These results demonstrate that CSP-1103 is neuroprotective in a model of post-ischemic brain injury and provide further mechanistic insights as regards its ability to reduce apoptosis and potential production of pro-inflammatory cytokines. In conclusion, these findings suggest a potential use of CSP-1103 for the treatment of brain ischemia. MDPI 2017-01-18 /pmc/articles/PMC5297816/ /pubmed/28106772 http://dx.doi.org/10.3390/ijms18010184 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Porrini, Vanessa Sarnico, Ilenia Benarese, Marina Branca, Caterina Mota, Mariana Lanzillotta, Annamaria Bellucci, Arianna Parrella, Edoardo Faggi, Lara Spano, Pierfranco Imbimbo, Bruno Pietro Pizzi, Marina Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title | Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title_full | Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title_fullStr | Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title_full_unstemmed | Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title_short | Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation |
title_sort | neuroprotective and anti-apoptotic effects of csp-1103 in primary cortical neurons exposed to oxygen and glucose deprivation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297816/ https://www.ncbi.nlm.nih.gov/pubmed/28106772 http://dx.doi.org/10.3390/ijms18010184 |
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