New perspectives on the role of the neurosteroid pregnenolone as an endogenous regulator of type‐1 cannabinoid receptor (CB1R) activity and function

Autor: Monique Vallée, Pierre-Louis Raux, Jean-Michel Revest, Guillaume Drutel
Přispěvatelé: INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), VALLEE, Monique, Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
medicine.medical_specialty
Allosteric modulator
Cannabinoid receptor
Neuroactive steroid
Type-1 cannabinoid receptor (CB1R)
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Allosteric regulation
Regulator
Biology
Steroid
03 medical and health sciences
Cellular and Molecular Neuroscience
GPCR
0302 clinical medicine
Endocrinology
Receptor
Cannabinoid
CB1
Internal medicine
medicine
Receptors
Cannabinoid
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
G protein-coupled receptor
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
0303 health sciences
Endocrine and Autonomic Systems
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
3. Good health
Biased signaling
Pregnenolone
Neurosteroids
Neuroscience
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Zdroj: Journal of Neuroendocrinology
Journal of Neuroendocrinology, Wiley, 2021, ⟨10.1111/jne.13034⟩
Journal of Neuroendocrinology, Wiley, 2022, Papers from the Virtual International Meeting STEROIDS and NERVOUS SYSTEM, TORINO, ITALY-February 2021, 34 (2), pp.e13034. ⟨10.1111/jne.13034⟩
ISSN: 0953-8194
1365-2826
DOI: 10.1111/jne.13034⟩
Popis: International audience; Pregnenolone is a steroid with specific characteristics, being the first steroid synthesized from cholesterol at all sites of steroidogenesis, including the brain. For many years, and even currently, pregnenolone was defined as an inactive precursor of all steroids, as no specific target had been discovered. But, over the last decade, it has become a steroid of interest since it has been recognized as being a biomarker for brain-related disorders through the development of metabolomic approaches and advanced analytical methods. In addition, physiological roles for pregnenolone emerged when specific targets were discovered. In this review, we will highlight the discovery of the selective interaction of pregnenolone with the type-1 cannabinoid receptor (CB1R). After describing the specific characteristic of CB1Rs, we will discuss the newly discovered mechanisms of their regulation by pregnenolone. In particular, we will describe the action of pregnenolone as a negative allosteric modulator (NAM) and a specific signaling inhibitor of the CB1R. These particular characteristics of pregnenolone provide a great strategic opportunity for therapeutic development in CB1-related Journal of Neuroendocrinology-Special issue Steroids & Nervous System 2021 2 disorders. Finally, we will outline new perspectives using innovative genetic tools for the discovery of original regulatory mechanisms of pregnenolone on CB1-related functions.
Databáze: OpenAIRE
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