Abstract
Intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. Thus, it is not surprising that altered synaptic morphology and function are involved in the molecular pathogenesis of so-called synaptopathies including autism, schizophrenia (SCZ) and Alzheimer's disease (AD). Intriguingly, various recent studies revealed a crucial role of postsynaptic ProSAP/Shank scaffold proteins in all of the aforementioned disorders. Considering these findings, we follow the hypothesis that ProSAP/Shank proteins are key regulators of synaptic development and plasticity with clear-cut isoform-specific roles. We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Brain / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology
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Child
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Child Development Disorders, Pervasive / metabolism
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Child Development Disorders, Pervasive / pathology
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Chromosome Deletion
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Chromosome Disorders / genetics
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Chromosome Disorders / metabolism
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Chromosomes, Human, Pair 22 / genetics
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Chromosomes, Human, Pair 22 / metabolism
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Humans
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Intellectual Disability / metabolism
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Intellectual Disability / pathology
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Models, Molecular
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Mutation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology
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Nervous System Diseases / genetics*
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Nervous System Diseases / pathology
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Neuronal Plasticity
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Schizophrenia / metabolism
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Schizophrenia / pathology
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Synapses / metabolism*
Substances
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Carrier Proteins
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Nerve Tissue Proteins
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SHANK2 protein, human
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SHANK3 protein, human
Supplementary concepts
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Telomeric 22q13 Monosomy Syndrome