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Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents
SGK1 is a serine/threonine kinase involved in several neurodegenerative-related pathways such as apoptosis, neuroinflammation, ionic channel regulation, and autophagy, among others. Despite its potential role as a pharmacological target against this kind of diseases, there are no reported inhibitors...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848319/ https://www.ncbi.nlm.nih.gov/pubmed/36637025 http://dx.doi.org/10.1080/14756366.2022.2153841 |
Sumario: | SGK1 is a serine/threonine kinase involved in several neurodegenerative-related pathways such as apoptosis, neuroinflammation, ionic channel regulation, and autophagy, among others. Despite its potential role as a pharmacological target against this kind of diseases, there are no reported inhibitors able to cross the BBB so far, being a field yet to be explored. In this context, a structure-based virtual screening against this kinase was performed, pointing out the deazapurine moiety as an interesting and easy-to-derivatize scaffold. Moreover, these inhibitors are able to i) exert neuroprotection in an in vitro model of AD and ii) block mitophagy in a PRKN-independent manner, reinforcing the hypothesis of SGK1 inhibitors as neuroprotective chemical tools. |
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