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Int. J. Mol. Sci. 2017, 18(1), 184; doi:10.3390/ijms18010184

Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation

1
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
2
Department of Neurorehabilitation, IRCCS San Camillo, Via Alberoni 70, 30126 Venice, Italy
3
Research & Development, Chiesi Farmaceutici, Via Palermo 26/A, 43100 Parma, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 11 October 2016 / Revised: 3 January 2017 / Accepted: 12 January 2017 / Published: 18 January 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2016)
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Abstract

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. View Full-Text
Keywords: CSP-1103; CHF5074; oxygen-glucose deprivation; ischemia; caspase-3; nuclear factor κB (NF-κB); p38; amyloid precursor protein intracellular domain (AICD) CSP-1103; CHF5074; oxygen-glucose deprivation; ischemia; caspase-3; nuclear factor κB (NF-κB); p38; amyloid precursor protein intracellular domain (AICD)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Porrini, V.; Sarnico, I.; Benarese, M.; Branca, C.; Mota, M.; Lanzillotta, A.; Bellucci, A.; Parrella, E.; Faggi, L.; Spano, P.; Imbimbo, B.P.; Pizzi, M. Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation. Int. J. Mol. Sci. 2017, 18, 184.

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