title: Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome.
abstract: OBJECTIVE
  A major challenge for understanding neurodevelopmental disorders, including autism spectrum disorders (ASDs), is to advance the findings from gene discovery to an exposition of neurobiological mechanisms that underlie these disorders and subsequently translate this knowledge into mechanism-based therapeutics. A promising way to proceed is revealed by the recent studies of rare subsets of ASDs. In this review, we summarize the latest advances in the mechanisms and emerging therapeutics for a rare single-gene ASD, Rett syndrome.
  
  
  RESULTS
  Rett syndrome is caused by mutations in the gene coding for methyl CpG-binding protein 2 (MeCP2). Although MeCP2 has diverse functions, examination of MeCP2 mutant mice suggests the hypothesis that MeCP2 deficiency leads to aberrant maturation and maintenance of synapses and circuits in multiple brain systems. Some of the deficits arise from alterations in specific intracellular pathways such as the PI3K/Akt signaling pathway. These abnormalities can be at least partially rescued in MeCP2 mutant mice by treatment with therapeutic agents.
  
  
  CONCLUSIONS
  Mechanism-based therapeutics are emerging for single-gene neurodevelopmental disorders such as Rett syndrome. Given the complexity of MeCP2 function, future directions include combination therapeutics that target multiple molecules and pathways. Such approaches will likely be applicable to other ASDs as well.
authors: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Jorge
authors: J
authors: Castro
authors: Nikolaos
authors: N
authors: Mellios
authors: Mriganka
authors: M
authors: Sur
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D015518:Rett Syndrome / Q000235:genetics* / Q000628:therapy; D013569:Synapses / Q000235:genetics
chemical_list: D051783:Methyl-CpG-Binding Protein 2