title: Role of Striatal-Enriched Tyrosine Phosphatase in Neuronal Function.
abstract: Striatal-enriched protein tyrosine phosphatase (STEP) is a CNS-enriched protein implicated in multiple neurologic and neuropsychiatric disorders. STEP regulates key signaling proteins required for synaptic strengthening as well as NMDA and AMPA receptor trafficking. Both high and low levels of STEP disrupt synaptic function and contribute to learning and behavioral deficits. High levels of STEP are present in human postmortem samples and animal models of Alzheimer's disease, Parkinson's disease, and schizophrenia and in animal models of fragile X syndrome. Low levels of STEP activity are present in additional disorders that include ischemia, Huntington's chorea, alcohol abuse, and stress disorders. Thus the current model of STEP is that optimal levels are required for optimal synaptic function. Here we focus on the role of STEP in Alzheimer's disease and the mechanisms by which STEP activity is increased in this illness. Both genetic lowering of STEP levels and pharmacological inhibition of STEP activity in mouse models of Alzheimer's disease reverse the biochemical and cognitive abnormalities that are present. These findings suggest that STEP is an important point for modulation of proteins required for synaptic plasticity.
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Marija
authors.identifier: 0000-0002-2664-2162
authors.initials: M
authors.lastname: Kamceva
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Jessie
authors.identifier: 0000-0002-8470-8764
authors.initials: J
authors.lastname: Benedict
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Angus C
authors.identifier: 0000-0002-7075-0195
authors.initials: AC
authors.lastname: Nairn
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lombroso
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C489930:PTPN5 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor