Synaptic proteins and receptors defects in autism spectrum disorders

Chen, Jianling; Yu, Shunying; Fu, Yingmei; Li, Xiaohong

doi:10.3389/fncel.2014.00276

Cited by 139 publications

(94 citation statements)

References 139 publications

(165 reference statements)

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“…MiR-873-5p binds to key genes for synapse formation and function including all three SHANK family members (SHANK1, SHANK2 and SHANK3), three Neuroligin family members (NLGN2, NLGN3 and NLGN4X), Discs Large MAGUK Scaffold Protein 4 (DLG4 also known as PSD95), and two DLG associated proteins (DLGAP3 and DLGAP4), which have been linked to ASD by multiple studies [47,76,77] (Fig. 3e, Supplementary Table 6).…”

Section: Convergence Of the Rare Regulatory And The Proteincoding Varmentioning

confidence: 99%

An integrative analysis of non-coding regulatory DNA variations associated with autism spectrum disorder

Williams

Edson

et al. 2018

Mol Psychiatry

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A number of genetic studies have identified rare protein-coding DNA variations associated with autism spectrum disorder (ASD), a neurodevelopmental disorder with significant genetic etiology and heterogeneity. In contrast, the contributions of functional, regulatory genetic variations that occur in the extensive non-protein-coding regions of the genome remain poorly understood. Here we developed a genome-wide analysis to identify the rare single nucleotide variants (SNVs) that occur in non-coding regions and determined the regulatory function and evolutionary conservation of these variants. Using publicly available datasets and computational predictions, we identified SNVs within putative regulatory regions in promoters, transcription factor binding sites, and microRNA genes and their target sites. Overall, we found that the regulatory variants in ASD cases were enriched in ASD-risk genes and genes involved in fetal neurodevelopment. As with previously reported coding mutations, we found an enrichment of the regulatory variants associated with dysregulation of neurodevelopmental and synaptic signaling pathways. Among these were several rare inherited SNVs found in the mature sequence of microRNAs predicted to affect the regulation of ASD-risk genes. We show a paternally inherited miR-873-5p variant with altered binding affinity for several risk-genes including NRXN2 and CNTNAP2 putatively overlay maternally inherited lossof-function coding variations in NRXN1 and CNTNAP2 to likely increase the genetic liability in an idiopathic ASD case. Our analysis pipeline provides a new resource for identifying loss-of-function regulatory DNA variations that may contribute to the genetic etiology of complex disorders.

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Section: Convergence Of the Rare Regulatory And The Proteincoding Varmentioning

confidence: 99%

An integrative analysis of non-coding regulatory DNA variations associated with autism spectrum disorder

Williams

Edson

et al. 2018

Mol Psychiatry

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“…49,[52][53][54][55] A structure located in glutamatergic synapses that has been associated with both disorders is the postsynaptic density (PSD). 50,[56][57][58][59][60][61] For example, Bayés and colleagues found that mutations in 199 human PSD genes were involved in more than 200 diseases, half being nervous-system disorders. 61 That study suggested that impairments in PSD proteins might underlie psychiatric disorders and their associated cognitive, behavioural and clinical phenotypes, but no systematic review based on this hypothesis has integrated the molecular data generated across studies in the last decade.…”

Section: J Psychiatry Neurosci 2018;43(4)mentioning

confidence: 99%

Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review

Soler

Fañanás

Parellada

et al. 2018

jpn

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“…25 ). Another important member of the neurexin family of proteins includes contactin-associated protein-like 2 (CNTNAP2), which is involved in neuron-glia interactions and clustering K + channels in myelinated axons 26 . Neuroligins are synaptic cell adhesion molecules that are enriched in postsynaptic membranes where they may recruit receptors, channels, and signal-transduction molecules 27 .…”

Section: Role Of the Cell Adhesion Molecules In Synapse Formationmentioning

confidence: 99%

“…Shank1-3 are synaptic scaffolding proteins that interact with a variety of membrane and cytoplasmic proteins. These proteins bind to neurexin-neuroligin complexes at postsynaptic excitatory glutamatergic synapses 26 . Specific positioning of Shank proteins at the postsynaptic sites of excitatory synapses suggests a role for this protein family in the organization of cytoskeletal/signaling complexes at specialized cell junctions 31 .…”

Section: Role Of the Scaffolding Proteins In Synapse Formationmentioning

confidence: 99%

“…Altered neuronal activity in ASD might be a reflection of disturbed synaptic integrity due to altered expression of cell adhesion and scaffolding molecules involved in synaptic development. Many of these molecules are associated with ASD, including neuroligins, neurexins, and Shank3 26 . In particular, alterations in the genes encoding neuroligins 3 and 4, their binding partners neurexins 1 and 3, Shanks and CNTNAP2 are implicated in synaptic changes in autism 38 .…”

Section: Synaptic Alterations In Autismmentioning

confidence: 99%

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Synapse alterations in autism: Review of animal model findings

Zatkova¹,

Bakoš²,

Hodosy³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Recent research has produced an explosion of experimental data on the complex neurobiological mechanisms of developmental disorders including autism. Animal models are one approach to studying the phenotypic features and molecular basis of autism. In this review, we describe progress in understanding synaptogenesis and alterations to this process with special emphasis on the cell adhesion molecules and scaffolding proteins implicated in autism. Genetic mouse model experiments are discussed in relation to alterations to selected synaptic proteins and consequent behavioral deficits measured in animal experiments. Methods. Pubmed databases were used to search for original and review articles on animal and human clinical studies on autism. Results. The cell adhesion molecules, neurexin, neurolignin and the Shank family of proteins are important molecular targets associated with autism. Conclusion. The heterogeneity of the autism spectrum of disorders limits interpretation of information acquired from any single animal model or animal test. We showed synapse-specific/ model-specific defects associated with a given genotype in these models. Characterization of mouse models with genetic variations may help study the mechanisms of autism in humans. However, it will be necessary to apply new analytic paradigms in using genetically modified mice for understanding autism etiology in humans. Further studies are needed to create animal models with mutations that match the molecular and neural bases of autism.

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Synaptic proteins and receptors defects in autism spectrum disorders

Cited by 139 publications

References 139 publications

An integrative analysis of non-coding regulatory DNA variations associated with autism spectrum disorder

An integrative analysis of non-coding regulatory DNA variations associated with autism spectrum disorder

Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review

Synapse alterations in autism: Review of animal model findings

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