title: Is the mTOR-signalling cascade disrupted in Schizophrenia?
abstract: The mammalian target of rapamycin (mTOR) signalling cascade is involved in the intracellular regulation of protein synthesis, specifically for proteins involved in controlling neuronal morphology and facilitating synaptic plasticity. Research has revealed that the activity of the mTOR cascade is influenced by several extracellular and environmental factors that have been implicated in schizophrenia. Therefore, there is reason to believe that one of the downstream consequences of dysfunction or hypofunction of these factors in schizophrenia is disrupted mTOR signalling and hence impaired protein synthesis. This results in abnormal neurodevelopment and deficient synaptic plasticity, outcomes which could underlie some of the positive, negative and cognitive symptoms of schizophrenia. This review will discuss the functional roles of the mTOR cascade and present evidence in support of a novel mTOR-based hypothesis of the neuropathology of schizophrenia. During neurodevelopment, genetic and epigenetic factors can disrupt mTOR signalling which affects synthesis of proteins essential for correct neuronal growth and network connectivity. This renders the CNS particularly vulnerable to the effects of secondary factors during adolescence which increases the risk of developing schizophrenia in adulthood. This review discusses the functional roles of the mTOR cascade and presents evidence in support of a novel mTOR-based hypothesis of the neuropathology of schizophrenia. Testing this hypothesis will advance our understanding of the aetiology of this illness and reveal novel therapeutic targets.
authors.affiliation: Behavioural Neuroscience Laboratory, The Florey Institute of Neuroscience & Mental Health, Parkville, Vic., Australia.
authors.forename: Anand
authors.initials: A
authors.lastname: Gururajan
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000818:Animals; D006801:Humans; D000091042:Reelin Protein; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000091042:Reelin Protein; D058570:TOR Serine-Threonine Kinases; C000717127:RELN protein, human
keywords: BDNF; Reelin; glutamate; mammalian target of rapamycin; schizophrenia