title: Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders.
abstract: With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.
authors.affiliation: Inserm CBT 1409, Centre d'Investigations Cliniques en Biothérapie, Marseille, France.|Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Féron
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: B
authors.initials: B
authors.lastname: Gepner
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Lacassagne
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: D
authors.initials: D
authors.lastname: Stephan
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: B
authors.initials: B
authors.lastname: Mesnage
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR 6231, Marseille, France.
authors.forename: M-P
authors.initials: MP
authors.lastname: Blanchard
authors.affiliation: Aix Marseille Université, TAGC UMR 1090, Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Boulanger
authors.affiliation: Aix Marseille Université, PsyCLE, EA 3273, Aix en Provence, France.
authors.forename: C
authors.initials: C
authors.lastname: Tardif
authors.affiliation: AP-HM, Département ORL, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Devèze
authors.affiliation: AP-HM, Département Anesthésie, Marseille, France.
authors.forename: S
authors.initials: S
authors.lastname: Rousseau
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Khrestchatisky
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Nivet
authors.affiliation: Aix Marseille Université, CNRS, NICN UMR 7259, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Erard-Garcia
mesh_terms: D000328:Adult; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D013466:Sulfurtransferases / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: C425823:MOCOS protein, human; D013466:Sulfurtransferases