[article]
| Titre : |
Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment |
| Type de document : |
texte imprimé |
| Auteurs : |
Joseph M. PALUMBO, Auteur ; Brian F. THOMAS, Auteur ; Dejan BUDIMIROVIC, Auteur ; Steven SIEGEL, Auteur ; Flora TASSONE, Auteur ; Randi HAGERMAN, Auteur ; Christopher FAULK, Auteur ; Stephen O'QUINN, Auteur ; Terri SEBREE, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Humans Fragile X Syndrome/drug therapy/genetics Cannabidiol/pharmacology/therapeutic use Endocannabinoids/metabolism Fragile X Mental Retardation Protein/genetics Cannabidiol Cannabinoid receptors Endocannabinoid system Fragile X syndrome development. BFT was a consultant to Zynerba Pharmaceuticals at the time of the manuscript development. DB was an investigator for the CONNECT-FX study for Zynerba Pharmaceuticals. SS is on the Scientific Advisory Board for fragile X syndrome for Zynerba Pharmaceuticals. FT and CF have no competing interests. RH has received funding from Zynerba Pharmaceuticals for the conduct of the study as an investigator and is on scientific advisory board for fragile X syndrome for Zynerba Pharmaceuticals. SO’Q and TS are employees of Zynerba Pharmaceuticals. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS). This review describes the ECS, its role in the central nervous system, how it is dysregulated in FXS, and the potential role of cannabidiol as a treatment for FXS. FXS is caused by deficiency or absence of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, typically due to the presence of >200 cytosine, guanine, guanine sequence repeats leading to methylation of the FMR1 gene promoter. The absence of FMRP, following FMR1 gene-silencing, disrupts ECS signaling, which has been implicated in FXS pathogenesis. The ECS facilitates synaptic homeostasis and plasticity through the cannabinoid receptor 1, CB(1), on presynaptic terminals, resulting in feedback inhibition of neuronal signaling. ECS-mediated feedback inhibition and synaptic plasticity are thought to be disrupted in FXS, leading to overstimulation, desensitization, and internalization of presynaptic CB(1) receptors. Cannabidiol may help restore synaptic homeostasis by acting as a negative allosteric modulator of CB(1), thereby attenuating the receptor overstimulation, desensitization, and internalization. Moreover, cannabidiol affects DNA methylation, serotonin 5HT(1A) signal transduction, gamma-aminobutyric acid receptor signaling, and dopamine D(2) and D(3) receptor signaling, which may contribute to beneficial effects in patients with FXS. Consistent with these proposed mechanisms of action of cannabidiol in FXS, in the CONNECT-FX trial the transdermal cannabidiol gel, ZYN002, was associated with improvements in measures of social avoidance, irritability, and social interaction, particularly in patients who are most affected, showing ≥90% methylation of the FMR1 gene. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-023-09475-z |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 |
in Journal of Neurodevelopmental Disorders > 15 (2023)
[article] Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment [texte imprimé] / Joseph M. PALUMBO, Auteur ; Brian F. THOMAS, Auteur ; Dejan BUDIMIROVIC, Auteur ; Steven SIEGEL, Auteur ; Flora TASSONE, Auteur ; Randi HAGERMAN, Auteur ; Christopher FAULK, Auteur ; Stephen O'QUINN, Auteur ; Terri SEBREE, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 15 (2023)
| Mots-clés : |
Humans Fragile X Syndrome/drug therapy/genetics Cannabidiol/pharmacology/therapeutic use Endocannabinoids/metabolism Fragile X Mental Retardation Protein/genetics Cannabidiol Cannabinoid receptors Endocannabinoid system Fragile X syndrome development. BFT was a consultant to Zynerba Pharmaceuticals at the time of the manuscript development. DB was an investigator for the CONNECT-FX study for Zynerba Pharmaceuticals. SS is on the Scientific Advisory Board for fragile X syndrome for Zynerba Pharmaceuticals. FT and CF have no competing interests. RH has received funding from Zynerba Pharmaceuticals for the conduct of the study as an investigator and is on scientific advisory board for fragile X syndrome for Zynerba Pharmaceuticals. SO’Q and TS are employees of Zynerba Pharmaceuticals. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS). This review describes the ECS, its role in the central nervous system, how it is dysregulated in FXS, and the potential role of cannabidiol as a treatment for FXS. FXS is caused by deficiency or absence of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, typically due to the presence of >200 cytosine, guanine, guanine sequence repeats leading to methylation of the FMR1 gene promoter. The absence of FMRP, following FMR1 gene-silencing, disrupts ECS signaling, which has been implicated in FXS pathogenesis. The ECS facilitates synaptic homeostasis and plasticity through the cannabinoid receptor 1, CB(1), on presynaptic terminals, resulting in feedback inhibition of neuronal signaling. ECS-mediated feedback inhibition and synaptic plasticity are thought to be disrupted in FXS, leading to overstimulation, desensitization, and internalization of presynaptic CB(1) receptors. Cannabidiol may help restore synaptic homeostasis by acting as a negative allosteric modulator of CB(1), thereby attenuating the receptor overstimulation, desensitization, and internalization. Moreover, cannabidiol affects DNA methylation, serotonin 5HT(1A) signal transduction, gamma-aminobutyric acid receptor signaling, and dopamine D(2) and D(3) receptor signaling, which may contribute to beneficial effects in patients with FXS. Consistent with these proposed mechanisms of action of cannabidiol in FXS, in the CONNECT-FX trial the transdermal cannabidiol gel, ZYN002, was associated with improvements in measures of social avoidance, irritability, and social interaction, particularly in patients who are most affected, showing ≥90% methylation of the FMR1 gene. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-023-09475-z |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 |
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