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PSD95: A synaptic protein implicated in schizophrenia or autism?

Austin A Coley1, Wen-Jun Gao1

  • 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, United States.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|November 25, 2017
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Summary

Postsynaptic density protein-95 (PSD-95) is crucial for brain development and synaptic function. Its disruption is linked to neurodevelopmental disorders like schizophrenia and autism, impacting cognition and learning.

Keywords:
AMPARAutismGlutamateNMDARNeurodevelopmentPSD-95Schizophrenia

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Neurodevelopmental Disorders

Background:

  • The postsynaptic density (PSD) is vital for excitatory synapse function.
  • Molecular components of the PSD are implicated in neurodevelopmental disorders like schizophrenia (SCZ) and autism.
  • Postsynaptic density protein-95 (PSD-95) is a key regulator of synaptic maturation.

Purpose of the Study:

  • To review the role of PSD-95 in synaptogenesis and neurodevelopment.
  • To discuss PSD-95 interactions with NMDA and AMPA receptors.
  • To explore how PSD-95 dysfunction contributes to SCZ and autism phenotypes.

Main Methods:

  • Literature review of existing studies on PSD-95.
  • Analysis of genomic and sequencing data in psychiatric patients.
  • Examination of animal models with PSD-95 deficiency.

Main Results:

  • PSD-95 interacts with and stabilizes N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs).
  • PSD-95 disruption is associated with cognitive deficits in SCZ and autism.
  • PSD-95 deficiency alters receptor composition and function, potentially contributing to neuropsychiatric pathologies.

Conclusions:

  • PSD-95 is essential for normal neurodevelopment and synaptic function.
  • Aberrations in PSD-95 are linked to the neuropathology of SCZ and autism.
  • Understanding PSD-95's role may offer new therapeutic strategies for these disorders.