Characterizing spine issues: If offers novel therapeutics to Angelman syndrome
- 7 May 2020
- journal article
- review article
- Published by Wiley in Developmental Neurobiology
- Vol. 80 (5-6), 200-209
- https://doi.org/10.1002/dneu.22757
Abstract
Angelman syndrome(AS) is a rare neurodevelopmental disorder characterized by severe mental retardation, microcephaly, speech impairment, frequent epilepsy, EEG abnormalities, ataxic movements, tongue protrusion, bursts of laughter, sleep abruptions, and hyperactivity. AS results from loss of function of the imprinted UBE3A (ubiquitin‐protein ligase E3A) gene on chromosome 15q11–q13, including a mutation on the maternal allele of Ube3a, a large deletion of the maternally inherited chromosomal region 15q11‐13, paternal uniparental disomy of chromosome 15q11‐13, or an imprinting defect. The Ube3a maternal deleted mouse model recaptured the major phenotypes of AS patients include seizure, learning and memory impairments, sleep disturbance and motor problems. Owing to the activity‐dependent structural and functional plasticity, dendritic spines are believed as the basic subcellular compartment for learning and memory and the sites where LTP and LTD are induced. Defects of spine formation and dynamics are common among several neurodevelopmental disorders and neuropsychiatric disorders including AS and reflect the underlying synaptopathology which drives clinically relevant behavioral deficits. This review will summarize the impaired spine density, morphology, and synaptic plasticity in AS and propose that future explorations on spine dynamics and synaptic plasticity may help develop novel interventions and therapy for neurodevelopmental disorders like AS.Keywords
This publication has 97 references indexed in Scilit:
- Maternal Loss of Ube3a Produces an Excitatory/Inhibitory Imbalance through Neuron Type-Specific Synaptic DefectsNeuron, 2012
- Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neuronsNature, 2011
- Dendritic spine pathology in neuropsychiatric disordersNature Neuroscience, 2011
- The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating ArcCell, 2010
- Ube3a is required for experience-dependent maturation of the neocortexNature Neuroscience, 2009
- Synaptic Signaling by All-Trans Retinoic Acid in Homeostatic Synaptic PlasticityNeuron, 2008
- A Drosophila model for Angelman syndromeProceedings of the National Academy of Sciences of the United States of America, 2008
- Rapid Translation of Arc/Arg3.1 Selectively Mediates mGluR-Dependent LTD through Persistent Increases in AMPAR Endocytosis RateNeuron, 2008
- Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunitProceedings of the National Academy of Sciences of the United States of America, 2007
- Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor TraffickingNeuron, 2006