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Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration
AIMS: Stroke has a high incidence and is a disabling condition that can lead to severe cognitive, motor, and sensory dysfunction. In this study, we employed a drug repurposing strategy to investigate the neuroprotective effect of lomitapide on focal ischemic brain injury and explore its potential me...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627359/ https://www.ncbi.nlm.nih.gov/pubmed/36052650 http://dx.doi.org/10.1111/cns.13961 |
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author | Zheng, Yangmin Hu, Yue Han, Ziping Yan, Feng Zhang, Sijia Yang, Zhenhong Zhao, Fangfang Li, Lingzhi Fan, Junfen Wang, Rongliang Luo, Yumin |
author_facet | Zheng, Yangmin Hu, Yue Han, Ziping Yan, Feng Zhang, Sijia Yang, Zhenhong Zhao, Fangfang Li, Lingzhi Fan, Junfen Wang, Rongliang Luo, Yumin |
author_sort | Zheng, Yangmin |
collection | PubMed |
description | AIMS: Stroke has a high incidence and is a disabling condition that can lead to severe cognitive, motor, and sensory dysfunction. In this study, we employed a drug repurposing strategy to investigate the neuroprotective effect of lomitapide on focal ischemic brain injury and explore its potential mechanism of action. METHODS: Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice and simulated by oxygen–glucose deprivation in N2a‐BV2 cells in co‐cultivation. RESULTS: Lomitapide significantly increased the survival rate, reduced the neuronal tissue loss, and improved the neurological function after MCAO. Furthermore, lomitapide could increase the expression of LC3‐II, reduce the expression of P62 and LAMP2, promote autophagic flux, and inhibit apoptosis by increasing and inhibiting the expression of the apoptosis‐associated proteins Bcl‐2 and Bax, respectively. In addition, lomitapide inhibited the migration of pro‐inflammatory microglia. CONCLUSION: Lomitapide is a lipid‐lowering drug, and this is the first study to explore its protective effect on ischemic nerve injury in vitro and in vivo. Our results suggest that lomitapide can be repositioned as a potential therapeutic drug for the treatment of stroke. |
format | Online Article Text |
id | pubmed-9627359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96273592022-11-03 Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration Zheng, Yangmin Hu, Yue Han, Ziping Yan, Feng Zhang, Sijia Yang, Zhenhong Zhao, Fangfang Li, Lingzhi Fan, Junfen Wang, Rongliang Luo, Yumin CNS Neurosci Ther Original Articles AIMS: Stroke has a high incidence and is a disabling condition that can lead to severe cognitive, motor, and sensory dysfunction. In this study, we employed a drug repurposing strategy to investigate the neuroprotective effect of lomitapide on focal ischemic brain injury and explore its potential mechanism of action. METHODS: Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice and simulated by oxygen–glucose deprivation in N2a‐BV2 cells in co‐cultivation. RESULTS: Lomitapide significantly increased the survival rate, reduced the neuronal tissue loss, and improved the neurological function after MCAO. Furthermore, lomitapide could increase the expression of LC3‐II, reduce the expression of P62 and LAMP2, promote autophagic flux, and inhibit apoptosis by increasing and inhibiting the expression of the apoptosis‐associated proteins Bcl‐2 and Bax, respectively. In addition, lomitapide inhibited the migration of pro‐inflammatory microglia. CONCLUSION: Lomitapide is a lipid‐lowering drug, and this is the first study to explore its protective effect on ischemic nerve injury in vitro and in vivo. Our results suggest that lomitapide can be repositioned as a potential therapeutic drug for the treatment of stroke. John Wiley and Sons Inc. 2022-09-02 /pmc/articles/PMC9627359/ /pubmed/36052650 http://dx.doi.org/10.1111/cns.13961 Text en © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zheng, Yangmin Hu, Yue Han, Ziping Yan, Feng Zhang, Sijia Yang, Zhenhong Zhao, Fangfang Li, Lingzhi Fan, Junfen Wang, Rongliang Luo, Yumin Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title | Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title_full | Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title_fullStr | Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title_full_unstemmed | Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title_short | Lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
title_sort | lomitapide ameliorates middle cerebral artery occlusion‐induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627359/ https://www.ncbi.nlm.nih.gov/pubmed/36052650 http://dx.doi.org/10.1111/cns.13961 |
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