Autism spectrum disorders: emerging mechanisms and mechanism-based treatment

• Published in: Frontiers in cellular neuroscience Vol. 9; p. 183
• Main Authors: Wang, Hansen, Doering, Laurie C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 12.05.2015; Frontiers Media S.A
• Subjects: Autism; Autism Spectrum Disorders; Brain-derived neurotrophic factor; Defects; Drug therapy; Fragile X Syndrome; Genes; Genetic engineering; Hippocampal plasticity; Hippocampus; Histone deacetylase; Hypoxia; Insects; Intellectual disabilities; MeCP2; MeCP2 protein; Methyl-CpG binding protein; Mutation; Neuroscience; Pathogenesis; Proteasomes; Proteins; Rett Syndrome; Roles; Studies; Synaptic plasticity; Treatment; Vitamin E; Canada; MeCP2; pathogenesis; treatment; FMRP; synaptic deficits; Rett syndrome; fragile X syndrome; autism spectrum disorders
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2015.00183

Westmark highlights a study which demonstrated how FMRP cooperates with other autism-related molecules in experience-dependent synaptic pruning through proteasome-mediated degradation of postsynaptic density 95 (PSD-95) and how that mechanism fails in fragile X syndrome (Tsai et al., 2012; Westmark, 2013). Janc and Muller report that the free radical scavenger Trolox attenuates neuronal hyperexcitability, restores synaptic plasticity, and improves hypoxia tolerance in the hippocampal slices of Mecp2−/y mice, suggesting that radical scavengers might be an option for treating neuronal dysfunction in Rett syndrome (Janc and Muller, 2014). Xu et al. report that the histone deacetylase-6 inhibitor Tubastatin-A improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice, demonstrating that histone deacetylase-6 is a potential pharmacological target for treating Rett syndrome (Xu et al., 2014). [...]Wang et al. provide a comprehensive review of current targeted pharmacological treatments for fragile X and Rett syndromes, and discuss related issues in both preclinical and clinical studies of potential therapies for ASDs (Wang et al., 2015). Since there are significant neurobiological overlaps among ASDs, the targeted treatments developed for fragile X and Rett syndromes will be highly relevant to other autistic disorders.