title: Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia.
abstract: Schizophrenia is a serious psychiatric illness which is experienced by about 1 % of individuals worldwide and has a debilitating impact on perception, cognition, and social function. Over the years, several models/hypotheses have been developed which link schizophrenia to dysregulations of the dopamine, glutamate, and serotonin receptor pathways. An important segment of these pathways that have been extensively studied for the pathophysiology of schizophrenia is the presynaptic neurotransmitter release mechanism. This set of molecular events is an evolutionarily well-conserved process that involves vesicle recruitment, docking, membrane fusion, and recycling, leading to efficient neurotransmitter delivery at the synapse. Accumulated evidence indicate dysregulation of this mechanism impacting postsynaptic signal transduction via different neurotransmitters in key brain regions implicated in schizophrenia. In recent years, after ground-breaking work that elucidated the operations of this mechanism, research efforts have focused on the alterations in the messenger RNA (mRNA) and protein expression of presynaptic neurotransmitter release molecules in schizophrenia and other neuropsychiatric conditions. In this review article, we present recent evidence from schizophrenia human postmortem studies that key proteins involved in the presynaptic release mechanism are dysregulated in the disorder. We also discuss the potential impact of dysfunctional presynaptic neurotransmitter release on the various neurotransmitter systems implicated in schizophrenia.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Chijioke N
authors.initials: CN
authors.lastname: Egbujo
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, NSW, 2031, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Sinclair
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. hahnc@exchange.upenn.edu.
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D051938:Munc18 Proteins / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000502:physiology; D050683:R-SNARE Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D017661:Receptors, Presynaptic / Q000502:physiology; D050600:SNARE Proteins / Q000502:physiology; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D015398:Signal Transduction / Q000502:physiology; D016704:Synapsins / Q000502:physiology; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology*; D016708:Synaptophysin / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25 / Q000502:physiology
chemical_list: D051938:Munc18 Proteins; D018377:Neurotransmitter Agents; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger; D017661:Receptors, Presynaptic; D050600:SNARE Proteins; C569014:SYP protein, human; D016704:Synapsins; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25
keywords: Complexin; Munc18; Neurotransmitter; Presynaptic; SNAP-25 (synaptosomal-associated protein 25); SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor); Schizophrenia; Synapsin; Synaptobrevin; Synaptophysin; Syntaxin