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

International Journal of Molecular Sciences

Marina Pizzi¹  Arianna Bellucci²  Lara Faggi²  Annamaria Lanzillotta²  Marina Benarese²  Ilenia Sarnico²  Caterina Branca²  Edoardo Parrella²  Vanessa Porrini²  Mariana Mota²  Pierfranco Spano²  Bruno Pietro Imbimbo³ 

[1] Development, Chiesi Farmaceutici, Via Palermo 26/A, 43100 Parma, Italy;Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy;;Research &

关键词: CSP-1103;    CHF5074;    oxygen-glucose deprivation;    ischemia;    caspase-3;    nuclear factor κB (NF-κB);    p38;    amyloid precursor protein intracellular domain (AICD);   

DOI  :  10.3390/ijms18010184

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown