Towards the convergent therapeutic potential of G protein‐coupled receptors in autism spectrum disorders
Abstract Autism spectrum disorders (ASDs) are diagnosed in 1/100 children 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 transduce extracell...
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| Published in | British journal of pharmacology Vol. 2023; pp. 1 - 24 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Wiley
07.09.2023
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| Subjects | |
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| Abstract | Abstract
Autism spectrum disorders (ASDs) are diagnosed in 1/100 children 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 transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V
1A
and V
1B
; metabotropic glutamate mGlu
5
and mGlu
7
; GABA
B2
; dopamine D
1
, D
2
and D
3
; serotoninergic 5‐HT
1B
; β
2
‐adrenoceptor; cholinergic M
3
; adenosine A
2A
and A
3
; angiotensin AT
2
; cannabinoid CB
1
; chemokine CX
3
CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5‐HT
2A
and 5‐HT
7
, for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D
2
, 5‐HT
2A
, CB
1
, OTR and V
1A
as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD. |
|---|---|
| AbstractList | Autism spectrum disorders (ASDs) are diagnosed in 1/100 children 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 cellsurface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V 1A and V 1B ; metabotropic glutamate mGlu 5 and mGlu 7 ; GABA B2 ; dopamine D 1 , D 2 and D 3 ; serotoninergic 5-HT 1B ; β 2-adrenoceptor; cholinergic M 3 ; adenosine A 2A and A 3 ; angiotensin AT 2 ; cannabinoid CB 1 ; chemokine CX 3 CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5-HT 2A and 5-HT 7 , for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D 2 , 5-HT 2A , CB 1 , OTR and V 1A as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD. Abstract Autism spectrum disorders (ASDs) are diagnosed in 1/100 children 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 transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V 1A and V 1B ; metabotropic glutamate mGlu 5 and mGlu 7 ; GABA B2 ; dopamine D 1 , D 2 and D 3 ; serotoninergic 5‐HT 1B ; β 2 ‐adrenoceptor; cholinergic M 3 ; adenosine A 2A and A 3 ; angiotensin AT 2 ; cannabinoid CB 1 ; chemokine CX 3 CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5‐HT 2A and 5‐HT 7 , for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D 2 , 5‐HT 2A , CB 1 , OTR and V 1A as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD. |
| Author | Crépieux, Pascale Annamneedi, Anil Bozon, Véronique Dudas, Ana Pellissier, Lucie P. Leray, Xavier Gora, Caroline |
| Author_xml | – sequence: 1 givenname: Anil orcidid: 0000-0002-6743-8627 surname: Annamneedi fullname: Annamneedi, Anil organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France, LE STUDIUM Loire Valley Institute for Advanced Studies Orléans France, Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology Kattankulathur Tamil Nadu India – sequence: 2 givenname: Caroline surname: Gora fullname: Gora, Caroline organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France – sequence: 3 givenname: Ana surname: Dudas fullname: Dudas, Ana organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France – sequence: 4 givenname: Xavier orcidid: 0000-0003-2107-6082 surname: Leray fullname: Leray, Xavier organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France, Inria, Inria Saclay‐Ile‐de‐France Palaiseau France – sequence: 5 givenname: Véronique surname: Bozon fullname: Bozon, Véronique organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France – sequence: 6 givenname: Pascale orcidid: 0000-0002-2712-5271 surname: Crépieux fullname: Crépieux, Pascale organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France, Inria, Inria Saclay‐Ile‐de‐France Palaiseau France – sequence: 7 givenname: Lucie P. orcidid: 0000-0001-7085-3242 surname: Pellissier fullname: Pellissier, Lucie P. organization: Team Biology of GPCR Signaling Systems (BIOS), CNRS, IFCE, INRAE Université de Tours Nouzilly France |
| BackLink | https://hal.science/hal-04220553$$DView record in HAL |
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| CitedBy_id | crossref_primary_10_3390_biomedicines12071402 crossref_primary_10_3390_ijms25126521 crossref_primary_10_1016_j_neubiorev_2024_105686 |
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| Keywords | social interaction G protein-coupled receptors signalling pathways autism spectrum disorder brain neurotransmitter |
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Autism spectrum disorders (ASDs) are diagnosed in 1/100 children worldwide, based on two core symptoms: deficits in social interaction and... Autism spectrum disorders (ASDs) are diagnosed in 1/100 children worldwide, based on two core symptoms: deficits in social interaction and communication, and... |
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| Title | Towards the convergent therapeutic potential of G protein‐coupled receptors in autism spectrum disorders |
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