title: Neurobiology of autism gene products: towards pathogenesis and drug targets.
abstract: BACKGROUND
  The genetic heterogeneity of autism spectrum disorders (ASDs) is enormous, and the neurobiology of proteins encoded by genes associated with ASD is very diverse. Revealing the mechanisms on which different neurobiological pathways in ASD pathogenesis converge may lead to the identification of drug targets.
  
  
  OBJECTIVE
  The main objective is firstly to outline the main molecular networks and neuronal mechanisms in which ASD gene products participate and secondly to answer the question how these converge. Finally, we aim to pinpoint drug targets within these mechanisms.
  
  
  METHODS
  Literature review of the neurobiological properties of ASD gene products with a special focus on the developmental consequences of genetic defects and the possibility to reverse these by genetic or pharmacological interventions.
  
  
  RESULTS
  The regulation of activity-dependent protein synthesis appears central in the pathogenesis of ASD. Through sequential consequences for axodendritic function, neuronal disabilities arise expressed as behavioral abnormalities and autistic symptoms in ASD patients. Several known ASD gene products have their effect on this central process by affecting protein synthesis intrinsically, e.g., through enhancing the mammalian target of rapamycin (mTOR) signal transduction pathway or through impairing synaptic function in general. These are interrelated processes and can be targeted by compounds from various directions: inhibition of protein synthesis through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation of synaptic activity.
  
  
  CONCLUSIONS
  ASD gene products may all feed into a central process of translational control that is important for adequate glutamatergic regulation of dendritic properties. This process can be modulated by available compounds but may also be targeted by yet unexplored routes.
authors.affiliation: Department Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3984 CG, Utrecht, The Netherlands.
authors.forename: Kristel T E
authors.initials: KT
authors.lastname: Kleijer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
authors.forename: Dilja D
authors.initials: DD
authors.lastname: Krueger
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourgeron
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: J Peter H
authors.initials: JP
authors.lastname: Burbach
mesh_terms: D000818:Animals; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D011506:Proteins