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Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
by
Delorme, Richard
, Chaste, Pauline
, Murray, Kerren
, Jamain, Stéphane
, Goubran-Botros, Hany
, Huguet, Guillaume
, Launay, Jean-Marie
, Pagan, Cécile
, Maronde, Erik
, Leboyer, Marion
, Benabou, Marion
, Amsellem, Frédérique
, Lemière, Nathalie
, Callebert, Jacques
, Fauchereau, Fabien
, Bourgeron, Thomas
in
14-3-3 protein
/ 14-3-3 Proteins - genetics
/ 14-3-3 Proteins - metabolism
/ 38/1
/ 38/23
/ 38/77
/ 631/208/366/1373
/ 631/378/1385
/ 631/378/87
/ 631/45/882
/ 692/699/476/1373
/ 82/16
/ Acetylserotonin O-Methyltransferase - metabolism
/ Adolescent
/ Adult
/ Aralkylamine N-acetyltransferase
/ Arylalkylamine N-Acetyltransferase - metabolism
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - metabolism
/ Blood Platelets - metabolism
/ Case-Control Studies
/ Child
/ Circadian rhythms
/ Cognitive science
/ Enzymatic activity
/ Female
/ Genetics
/ Glands
/ Heterogeneity
/ Human health and pathology
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - metabolism
/ Life Sciences
/ Male
/ Melatonin
/ Melatonin - biosynthesis
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Middle Aged
/ multidisciplinary
/ N-Acetylserotonin
/ Pineal gland
/ Pineal Gland - metabolism
/ Platelets
/ Post-transcription
/ Post-translation
/ Psychiatrics and mental health
/ Science
/ Science (multidisciplinary)
/ Serotonin
/ Transcription
2017
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Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
by
Delorme, Richard
, Chaste, Pauline
, Murray, Kerren
, Jamain, Stéphane
, Goubran-Botros, Hany
, Huguet, Guillaume
, Launay, Jean-Marie
, Pagan, Cécile
, Maronde, Erik
, Leboyer, Marion
, Benabou, Marion
, Amsellem, Frédérique
, Lemière, Nathalie
, Callebert, Jacques
, Fauchereau, Fabien
, Bourgeron, Thomas
in
14-3-3 protein
/ 14-3-3 Proteins - genetics
/ 14-3-3 Proteins - metabolism
/ 38/1
/ 38/23
/ 38/77
/ 631/208/366/1373
/ 631/378/1385
/ 631/378/87
/ 631/45/882
/ 692/699/476/1373
/ 82/16
/ Acetylserotonin O-Methyltransferase - metabolism
/ Adolescent
/ Adult
/ Aralkylamine N-acetyltransferase
/ Arylalkylamine N-Acetyltransferase - metabolism
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - metabolism
/ Blood Platelets - metabolism
/ Case-Control Studies
/ Child
/ Circadian rhythms
/ Cognitive science
/ Enzymatic activity
/ Female
/ Genetics
/ Glands
/ Heterogeneity
/ Human health and pathology
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - metabolism
/ Life Sciences
/ Male
/ Melatonin
/ Melatonin - biosynthesis
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Middle Aged
/ multidisciplinary
/ N-Acetylserotonin
/ Pineal gland
/ Pineal Gland - metabolism
/ Platelets
/ Post-transcription
/ Post-translation
/ Psychiatrics and mental health
/ Science
/ Science (multidisciplinary)
/ Serotonin
/ Transcription
2017
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Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
by
Delorme, Richard
, Chaste, Pauline
, Murray, Kerren
, Jamain, Stéphane
, Goubran-Botros, Hany
, Huguet, Guillaume
, Launay, Jean-Marie
, Pagan, Cécile
, Maronde, Erik
, Leboyer, Marion
, Benabou, Marion
, Amsellem, Frédérique
, Lemière, Nathalie
, Callebert, Jacques
, Fauchereau, Fabien
, Bourgeron, Thomas
in
14-3-3 protein
/ 14-3-3 Proteins - genetics
/ 14-3-3 Proteins - metabolism
/ 38/1
/ 38/23
/ 38/77
/ 631/208/366/1373
/ 631/378/1385
/ 631/378/87
/ 631/45/882
/ 692/699/476/1373
/ 82/16
/ Acetylserotonin O-Methyltransferase - metabolism
/ Adolescent
/ Adult
/ Aralkylamine N-acetyltransferase
/ Arylalkylamine N-Acetyltransferase - metabolism
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - metabolism
/ Blood Platelets - metabolism
/ Case-Control Studies
/ Child
/ Circadian rhythms
/ Cognitive science
/ Enzymatic activity
/ Female
/ Genetics
/ Glands
/ Heterogeneity
/ Human health and pathology
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - metabolism
/ Life Sciences
/ Male
/ Melatonin
/ Melatonin - biosynthesis
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Middle Aged
/ multidisciplinary
/ N-Acetylserotonin
/ Pineal gland
/ Pineal Gland - metabolism
/ Platelets
/ Post-transcription
/ Post-translation
/ Psychiatrics and mental health
/ Science
/ Science (multidisciplinary)
/ Serotonin
/ Transcription
2017
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Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
Journal Article
Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
2017
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Overview
Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands - the main source of melatonin (9 patients and 22 controls) - and gut samples - the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3ζ) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14-3-3 Proteins - metabolism
/ 38/1
/ 38/23
/ 38/77
/ 82/16
/ Acetylserotonin O-Methyltransferase - metabolism
/ Adult
/ Aralkylamine N-acetyltransferase
/ Arylalkylamine N-Acetyltransferase - metabolism
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - metabolism
/ Blood Platelets - metabolism
/ Child
/ Female
/ Genetics
/ Glands
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - metabolism
/ Male
/ Psychiatrics and mental health
/ Science
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