{"language":[{"iso":"eng"}],"date_created":"2021-11-14T23:01:24Z","publication_identifier":{"eissn":["2073-4425"]},"file_date_updated":"2022-05-16T07:02:27Z","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","article_processing_charge":"No","day":"30","issue":"11","intvolume":"        12","project":[{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","publisher":"MDPI","article_type":"original","article_number":"1746","file":[{"success":1,"access_level":"open_access","file_id":"11380","relation":"main_file","file_name":"2021_Genes_Vasic.pdf","content_type":"application/pdf","date_updated":"2022-05-16T07:02:27Z","file_size":1335308,"date_created":"2022-05-16T07:02:27Z","creator":"dernst","checksum":"256cb832a9c3051c7dc741f6423b8cbd"}],"department":[{"_id":"GaNo"}],"date_published":"2021-10-30T00:00:00Z","oa_version":"Published Version","ec_funded":1,"abstract":[{"lang":"eng","text":"Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems"}],"oa":1,"date_updated":"2023-08-14T11:46:12Z","has_accepted_license":"1","author":[{"first_name":"Verica","last_name":"Vasic","full_name":"Vasic, Verica"},{"last_name":"Jones","first_name":"Mattson S.O.","full_name":"Jones, Mattson S.O."},{"id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","last_name":"Haslinger","first_name":"Denise","full_name":"Haslinger, Denise"},{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","full_name":"Knaus, Lisa"},{"first_name":"Michael J.","last_name":"Schmeisser","full_name":"Schmeisser, Michael J."},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Chiocchetti, Andreas G.","first_name":"Andreas G.","last_name":"Chiocchetti"}],"external_id":{"isi":["000834044200002"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10281","year":"2021","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"quality_controlled":"1","doi":"10.3390/genes12111746","publication_status":"published","isi":1,"citation":{"chicago":"Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>.","ama":"Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. 2021;12(11). doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>","apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., &#38; Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>","ieee":"V. Vasic <i>et al.</i>, “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” <i>Genes</i>, vol. 12, no. 11. MDPI, 2021.","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","ista":"Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>, vol. 12, no. 11, 1746, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>."},"publication":"Genes","month":"10","scopus_import":"1","ddc":["570"],"volume":12,"acknowledgement":"This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811); Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was also supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24) both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes for her support in preparing this manuscript.","status":"public"}