title: Current Perspectives in Autism Spectrum Disorder: From Genes to Therapy.
abstract: Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with high heritability and both phenotypic and genetic heterogeneity. To date, mutations in hundreds of genes have been associated to varying degrees with increased ASD risk. A better understanding of the functions of these genes and whether they fit together in functional groups or impact similar neuronal circuits is needed to develop rational treatment strategies. We will review current areas of emphasis in ASD research, starting from human genetics and exploring how mouse models of human mutations have helped identify specific molecular pathways (protein synthesis and degradation, chromatin remodeling, intracellular signaling), which are linked to alterations in circuit function and cognitive/social behavior. We will conclude by discussing how we can leverage the findings on molecular and cellular alterations found in ASD to develop therapies for neurodevelopmental disorders.
authors.affiliation: Eugene McDermott Center for Human Growth and Development, Departments of Neuroscience and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, cmanzini@gwu.edu Maria.Chahrour@utsouthwestern.edu.
authors.forename: Maria
authors.identifier: 0000-0002-3174-1480
authors.initials: M
authors.lastname: Chahrour
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Brian J
authors.identifier: 0000-0002-4141-0095
authors.initials: BJ
authors.lastname: O'Roak
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Santini
authors.affiliation: Department of Molecular and Human Genetics, Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030.
authors.forename: Rodney C
authors.initials: RC
authors.lastname: Samaco
authors.affiliation: Translational Neuroscience Center, F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, and.
authors.forename: Robin J
authors.identifier: 0000-0002-9415-7433
authors.initials: RJ
authors.lastname: Kleiman
authors.affiliation: Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037 cmanzini@gwu.edu Maria.Chahrour@utsouthwestern.edu.
authors.forename: M Chiara
authors.identifier: 0000-0001-7175-1096
authors.initials: MC
authors.lastname: Manzini
mesh_terms: D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D001921:Brain / Q000378:metabolism*; D019317:Evidence-Based Medicine; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D009419:Nerve Tissue Proteins
keywords: animal models; autism spectrum disorder; genetics; therapeutics