Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes
| Autor: | Delaitre, Céline, Boisbrun, Michel, Lecat, Sandra, DUPUIS, François |
|---|---|
| Přispěvatelé: | Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Ang-(1–7)
QH301-705.5 Review [CHIM.THER]Chemical Sciences/Medicinal Chemistry Receptor Angiotensin Type 1 Brain Injuries Traumatic Sciences du Vivant [q-bio]/Biologie cellulaire Animals Humans Molecular Targeted Therapy Sciences du Vivant [q-bio]/Sciences pharmaceutiques Biology (General) QD1-999 beta-Arrestins beta-arrestin AT1 receptor [CHIM.ORGA]Chemical Sciences/Organic chemistry Angiotensin II Intracranial Aneurysm cerebrovascular disease Stroke Chemistry biased agonism Cardiovascular Diseases TRV023 Angiotensin II Type 1 Receptor Blockers hormones hormone substitutes and hormone antagonists Signal Transduction TRV027 RAS |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 6738, p 6738 (2021) International Journal of Molecular Sciences International Journal of Molecular Sciences, MDPI, 2021, 22 (13), pp.6738. ⟨10.3390/ijms22136738⟩ |
| ISSN: | 1661-6596 1422-0067 |
| DOI: | 10.3390/ijms22136738⟩ |
| Popis: | The physiological and pathophysiological relevance of the angiotensin II type 1 (AT1) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT1 receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT1 in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT1 signaling and the development of biased AT1 agonists, able to selectively activate the β-arrestin transduction pathway rather than the Gq pathway, have led to new therapeutic strategies to target detrimental effects of AT1 activation. In this paper, we review the involvement of AT1 in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT1 agonists could be considered as new therapeutic avenues for cerebrovascular diseases. |
| Databáze: | OpenAIRE |
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