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Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders
  • +4
  • Anil Annamneedi,
  • Caroline Gora,
  • Ana Dudas,
  • Xavier Leray,
  • Véronique Bozon,
  • Pascale Crepieux,
  • Lucie P. Pellissier
Anil Annamneedi
Physiologie de la Reproduction et des Comportements
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Caroline Gora
Physiologie de la Reproduction et des Comportements
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Ana Dudas
Physiologie de la Reproduction et des Comportements
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Xavier Leray
Physiologie de la Reproduction et des Comportements
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Véronique Bozon
Physiologie de la Reproduction et des Comportements
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Pascale Crepieux
Physiologie de la Reproduction et des Comportements
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Lucie P. Pellissier
Physiologie de la Reproduction et des Comportements

Corresponding Author:[email protected]

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Abstract

Autism spectrum disorders (ASD) are diagnosed in 1/100 childbirth worldwide, based on two core symptoms, deficits in social interaction and communication and stereotyped behaviours. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors that mediate the transfer of extracellular signals to convergent intracellular signalling and downstream cellular responses that are dysregulated in ASD. Despite hundreds of GPCRs are expressed in the brain, only 23 GPCRs are genetically associated to ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR, vasopressin V1A, V1B, metabotropic glutamate mGlu5, mGlu7, GABAB, dopamine D1, D2, D3, serotoninergic 5-HT1B, β2-adrenoceptor, cholinergic M3, adenosine A2A, A3, angiotensin AT2, cannabinoid CB1, chemokine CX3CR1, orphan GPR37, GPR85 and olfactory OR1C1, OR2M4, OR2T10, OR52M1. Here, we review the therapeutical potential of these 23 GPCRs, in addition to 5-HT2A, 5-HT6 and 5-HT7 for their relevance to ASD. We discuss their genetic association with ASD, the effects of their genetic and pharmacological manipulation in animal models and humans, their existing pharmacopeia towards core symptoms of ASD and rank them based on these evidences. Among these 23 GPCRs, we highlight that OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 are the best therapeutic targets. We conclude that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD and their therapeutic potential has only begun as multiple GPCRs could mitigate ASD.
22 Feb 2023Submitted to British Journal of Pharmacology
23 Feb 2023Submission Checks Completed
23 Feb 2023Assigned to Editor
06 Mar 2023Reviewer(s) Assigned
18 Apr 2023Review(s) Completed, Editorial Evaluation Pending
17 May 2023Editorial Decision: Revise Minor
01 Jul 20231st Revision Received
03 Jul 2023Submission Checks Completed
03 Jul 2023Assigned to Editor
04 Jul 2023Reviewer(s) Assigned
02 Aug 2023Review(s) Completed, Editorial Evaluation Pending
02 Aug 2023Editorial Decision: Accept