RAUX, Pierre-Louis; DRUTEL, Guillaume; REVEST, Jean-Michel; VALLEE, Monique

doi:10.1111/jne.13034

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

DRUTEL, Guillaume

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

REVEST, Jean-Michel

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Ce document a été publié dans

Journal of Neuroendocrinology. 2022-02, vol. 34, n° 2

Résumé en anglais

Pregnenolone is a steroid with specific characteristics, being the first steroid to be synthesised from cholesterol at all sites of steroidogenesis, including the brain. For many years, pregnenolone was defined as an inactive precursor of all steroids because no specific target had been discovered. However, over the last decade, it has become a steroid of interest because it has been recognised 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 highlight the discovery of the selective interaction of pregnenolone with the type-1 cannabinoid receptor (CB1R). After describing the specific characteristic of CB1Rs, we discuss the newly discovered mechanisms of their regulation by pregnenolone. In particular, we describe the action of pregnenolone as a negative allosteric modulator and a specific signalling inhibitor of the CB1R. These particular characteristics of pregnenolone provide a great strategic opportunity for therapeutic development in CB1-related disorders. Finally, we outline new perspectives using innovative genetic tools for the discovery of original regulatory mechanisms of pregnenolone on CB1-related functions.< Réduire

Mots clés en anglais

Allosteric regulation

Biased signalling

GPCR

Neurosteroids

Pregnenolone

Type-1 cannabinoid receptor (CB1R)

URI

https://oskar-bordeaux.fr/handle/20.500.12278/136582

DOI

http://dx.doi.org/10.1111/jne.13034

Unités de recherche

Neurocentre Magendie - U1215

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

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Résumé en anglais

Mots clés en anglais

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Unités de recherche