Nov 25, 2017

PSD95: A synaptic protein implicated in schizophrenia or autism?

Progress in Neuro-psychopharmacology & Biological Psychiatry
Austin A Coley, Wen-Jun Gao


The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism. For instance, recent genomic and sequencing studies of psychiatric patients highlight the aberrations at the PSD of glutamatergic synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency shows alterations in NMDA and AMPA-receptor composition and function in specific brain regions that may contribute to phenotypes observed in neuropsychiatric pathologies. In this review, we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment. More specifically, we discuss its interactions with NMDA receptor subunits that po...Continue Reading

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Mentioned in this Paper

Receptors, Amino Acid
Grin3a protein, rat
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Presynaptic density protein 95
Postsynaptic Density Organization

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