Cellular and Molecular Mechanisms of R/S-Roscovitine and CDKs Related Inhibition under Both Focal and Global Cerebral Ischemia: A Focus on Neurovascular Unit and Immune Cells
| Autor: | Serge Timsit, Ahmed Amara, Cloé Le Roux, Lucas Le Roy, Anne Létondor |
|---|---|
| Přispěvatelé: | Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), PODEUR, Sophie |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
CDK Ischemia Inflammation Review Pharmacology Models Biological Brain Ischemia Immune system leucocytes Cyclin-dependent kinase Leukocytes medicine ischemic stroke Animals Humans neurovascular unit roscovitine lcsh:QH301-705.5 biology Kinase business.industry Brain General Medicine medicine.disease Neurovascular bundle Cyclin-Dependent Kinases Peripheral [SDV] Life Sciences [q-bio] lcsh:Biology (General) biology.protein medicine.symptom business Infiltration (medical) |
| Zdroj: | Cells, Vol 10, Iss 104, p 104 (2021) Cells Cells, MDPI, 2021, 10 (1), pp.104. ⟨10.3390/cells10010104⟩ |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10010104⟩ |
| Popis: | International audience; Ischemic stroke is the second leading cause of death worldwide. Following ischemic stroke, Neurovascular Unit (NVU) inflammation and peripheral leucocytes infiltration are major contributors to the extension of brain lesions. For a long time restricted to neurons, the 10 past years have shown the emergence of an increasing number of studies focusing on the role of Cyclin-Dependent Kinases (CDKs) on the other cells of NVU, as well as on the leucocytes. The most widely used CDKs inhibitor, (R)-roscovitine, and its (S) isomer both decreased brain lesions in models of global and focal cerebral ischemia. We previously showed that (S)-roscovitine acted, at least, by modulating NVU response to ischemia. Interestingly, roscovitine was shown to decrease leucocytes-mediated inflammation in several inflammatory models. Specific inhibition of roscovitine majors target CDK 1, 2, 5, 7, and 9 showed that these CDKs played key roles in inflammatory processes of NVU cells and leucocytes after brain lesions, including ischemic stroke. The data summarized here support the investigation of roscovitine as a potential therapeutic agent for the treatment of ischemic stroke, and provide an overview of CDK 1, 2, 5, 7, and 9 functions in brain cells and leucocytes during cerebral ischemia. |
| Databáze: | OpenAIRE |
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