tyrosine 3 monooxygenase

Summary

Summary: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.

Top Publications

  1. ncbi 14-3-3 proteins: structure, function, and regulation
    H Fu
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Pharmacol Toxicol 40:617-47. 2000
  2. ncbi Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development
    Soojin Ryu
    Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D 79104 Freiburg, Germany
    Curr Biol 17:873-80. 2007
  3. ncbi The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives
    A Pattyn
    Laboratoire de Genetique et Physiologie du Developpement, Developmental Biology Institute of Marseille, CNRS INSERM Université de la Méditterranée AP de Marseille, France
    Nature 399:366-70. 1999
  4. ncbi Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease
    Jin Xu
    Department of Neurology, Harvard Medical School and Division of Neuroscience, The Children s Hospital, Boston, Massachusetts, USA
    Nat Med 8:600-6. 2002
  5. pmc 14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts
    A Kumagai
    Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA
    Mol Biol Cell 9:345-54. 1998
  6. ncbi The structural basis for 14-3-3:phosphopeptide binding specificity
    M B Yaffe
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Cell 91:961-71. 1997
  7. ncbi Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding
    K Rittinger
    Divison of Protein Structure, National Institute for Medical Research, London, United Kingdom
    Mol Cell 4:153-66. 1999
  8. ncbi Development of chromaffin cells depends on MASH1 function
    Katrin Huber
    Neuroanatomy, Interdisciplinary Center for Neurosciences IZN, University of Heidelberg, INF 307, D 69120 Heidelberg, Germany
    Development 129:4729-38. 2002
  9. ncbi c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice
    K Burau
    Interdisciplinary Center for Neurosciences, Department of Neuroanatomy, University of Heidelberg, INF 307, D 69120 Heidelberg, Germany
    Eur J Neurosci 20:353-62. 2004
  10. ncbi 14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin
    Antje Gohla
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Biol 12:1704-10. 2002

Research Grants

Detail Information

Publications263 found, 100 shown here

  1. ncbi 14-3-3 proteins: structure, function, and regulation
    H Fu
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Pharmacol Toxicol 40:617-47. 2000
    ..In this review, we examine the structural basis for 14-3-3-ligand interactions, proposed functions of 14-3-3 in various signaling pathways, and emerging views of mechanisms that regulate 14-3-3 actions...
  2. ncbi Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development
    Soojin Ryu
    Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D 79104 Freiburg, Germany
    Curr Biol 17:873-80. 2007
    ..Thus, Otp is one of the few known transcription factors that can determine aspects of the dopaminergic phenotype and the first known factor to control the development of the diencephalospinal dopaminergic system...
  3. ncbi The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives
    A Pattyn
    Laboratoire de Genetique et Physiologie du Developpement, Developmental Biology Institute of Marseille, CNRS INSERM Université de la Méditterranée AP de Marseille, France
    Nature 399:366-70. 1999
    ....
  4. ncbi Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease
    Jin Xu
    Department of Neurology, Harvard Medical School and Division of Neuroscience, The Children s Hospital, Boston, Massachusetts, USA
    Nat Med 8:600-6. 2002
    ..Thus, accumulation of soluble alpha-synuclein protein complexes can render endogenous dopamine toxic, suggesting a potential mechanism for the selectivity of neuronal loss in PD...
  5. pmc 14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts
    A Kumagai
    Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA
    Mol Biol Cell 9:345-54. 1998
    ..These findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition...
  6. ncbi The structural basis for 14-3-3:phosphopeptide binding specificity
    M B Yaffe
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Cell 91:961-71. 1997
    ..Finally, we show that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD, and Cbl...
  7. ncbi Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding
    K Rittinger
    Divison of Protein Structure, National Institute for Medical Research, London, United Kingdom
    Mol Cell 4:153-66. 1999
    ..Structural homology between the 14-3-3 NES structure and those within I kappa B alpha and p53 reveals a conserved topology recognized by the Crm1 nuclear export machinery...
  8. ncbi Development of chromaffin cells depends on MASH1 function
    Katrin Huber
    Neuroanatomy, Interdisciplinary Center for Neurosciences IZN, University of Heidelberg, INF 307, D 69120 Heidelberg, Germany
    Development 129:4729-38. 2002
    ..Together, these findings suggest that the development of chromaffin cells does depend on MASH1 function not only for catecholaminergic differentiation but also for general chromaffin cell differentiation...
  9. ncbi c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice
    K Burau
    Interdisciplinary Center for Neurosciences, Department of Neuroanatomy, University of Heidelberg, INF 307, D 69120 Heidelberg, Germany
    Eur J Neurosci 20:353-62. 2004
    ..Our data suggest that c-ret signalling is necessary for the maturation of cholinergic sympathetic neurons but dispensable for de novo induction of ChAT and VAChT expression...
  10. ncbi 14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin
    Antje Gohla
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Biol 12:1704-10. 2002
    ..Taken together, these results suggest that 14-3-3zeta proteins may play a dynamic role in the regulation of cellular actin structures through the maintenance of phosphocofilin levels...
  11. pmc TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
    F Kanai
    Division of Signal Transduction, Department of Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 19:6778-91. 2000
    ..TAZ may link events at the plasma membrane and cytoskeleton to nuclear transcription in a manner that can be regulated by 14-3-3...
  12. pmc Protein kinase C delta negatively regulates tyrosine hydroxylase activity and dopamine synthesis by enhancing protein phosphatase-2A activity in dopaminergic neurons
    Danhui Zhang
    Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, Iowa 50011, USA
    J Neurosci 27:5349-62. 2007
    ..Collectively, these results suggest that PKCdelta phosphorylates PP2Ac to enhance its activity and thereby reduces TH-ser40 phosphorylation and TH activity and ultimately dopamine synthesis...
  13. ncbi Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease
    J H Kordower
    Department of Neurological Sciences, Rush Presbyterian St Luke s Medical Center, Chicago, IL 60612, USA
    Science 290:767-73. 2000
    ..These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients...
  14. ncbi 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation
    Guri Tzivion
    Cardiovascular Research Institute, Division of Molecular Cardiology, Texas A and M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA
    J Biol Chem 277:3061-4. 2002
  15. ncbi Ontogeny and innervation patterns of dopaminergic, noradrenergic, and serotonergic neurons in larval zebrafish
    David L McLean
    Department of Neurobiology and Behavior, Life Sciences Building, State University of New York at Stony Brook, Stony Brook, New York 11794 5230, USA
    J Comp Neurol 480:38-56. 2004
    ..Our results suggest that the major aminergic systems described in adults are in place shortly after hatching, at a time when zebrafish are accessible to a battery of techniques to test neuronal function during behavior...
  16. ncbi Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders
    E Masliah
    Department of Neurosciences, Department of Pathology, University of California San Diego, La Jolla, CA 92093 0624, USA
    Science 287:1265-9. 2000
    ..These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions...
  17. ncbi Particular subpopulations of midbrain and hypothalamic dopamine neurons express vesicular glutamate transporter 2 in the rat brain
    Michihiro Kawano
    Laboratory of Neuroendocrinology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305 8575, Japan
    J Comp Neurol 498:581-92. 2006
    ..These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons...
  18. ncbi Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner
    Kwang Soo Kim
    Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
    J Neurochem 85:622-34. 2003
    ..Our results suggest that Nurr1 may play a direct role for specification of DA neurotransmitter identity by activating TH gene transcription in a cell context-dependent manner...
  19. ncbi Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein
    A Lopez-Girona
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 397:172-5. 1999
    ..Thus, Rad24 appears to function as an attachable nuclear-export signal that enhances the nuclear export of Cdc25 in response to DNA damage...
  20. ncbi Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio)
    J Kaslin
    Department of Biology, Abo Akademi University, BioCity, FIN-20520 Turku/Abo, Finland
    J Comp Neurol 440:342-77. 2001
    ..The results also provide evidence of homologies to mammalian systems and allow identification of several previously uncharacterized systems in zebrafish mutants...
  21. pmc Glutamatergic neurons are present in the rat ventral tegmental area
    Tsuyoshi Yamaguchi
    National Institute on Drug Abuse, Cellular Neurophysiology, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    Eur J Neurosci 25:106-18. 2007
    ..Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic...
  22. ncbi Dopamine depletion impairs precursor cell proliferation in Parkinson disease
    Günter U Höglinger
    INSERM U289 Hôpital de la Salpetrière, F 75651 Paris, France
    Nat Neurosci 7:726-35. 2004
    ..These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation...
  23. ncbi Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols
    Ran Barzilay
    Laboratory of Neurosciences, Felsenstein Medical Research Center, Petah Tiqwa, 49100 Israel
    Stem Cells Dev 17:547-54. 2008
    ..Moreover, the induced cells secreted dopamine in response to depolarization. These results demonstrate the great therapeutic potential of human MSCs in PD...
  24. pmc Regulation of histone deacetylase 4 by binding of 14-3-3 proteins
    A H Wang
    Molecular Oncology Group, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
    Mol Cell Biol 20:6904-12. 2000
    ..These results indicate that 14-3-3 proteins negatively regulate HDAC4 by preventing its nuclear localization and thereby uncover a novel regulatory mechanism for HDACs...
  25. pmc Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome
    James R Connor
    Department of Neurosurgery, Penn State College of Medicine, Hershey, PA 17033 0850, USA
    Brain 132:2403-12. 2009
    ..The results are consistent with the hypothesis that a primary iron insufficiency produces a dopaminergic abnormality characterized as an overly activated dopaminergic system as part of the RLS pathology...
  26. ncbi Stoichiometry of tyrosine hydroxylase phosphorylation in the nigrostriatal and mesolimbic systems in vivo: effects of acute haloperidol and related compounds
    M F Salvatore
    Department of Biochemistry and Molecular Biology and Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
    J Neurochem 75:225-32. 2000
    ....
  27. ncbi Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in vitro and in vivo
    Lilla M Farkas
    Neuroanatomy, Interdisciplinary Center for Neurosciences, University of Heidelberg, D 69120 Heidelberg, Germany
    J Neurosci 23:5178-86. 2003
    ..Together, our results identify TGF-beta as an essential mediator for the induction and maintenance of midbrain dopaminergic neurons...
  28. ncbi Detection of behavioral impairments correlated to neurochemical deficits in mice treated with moderate doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
    Jennifer L Tillerson
    Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA
    Exp Neurol 178:80-90. 2002
    ..Detection of dopamine-modulated behavioral changes in moderately depleted MPTP mice will allow for more efficacious use of this model in PD research...
  29. ncbi Dynamics of tyrosine hydroxylase promoter activity during midbrain dopaminergic neuron development
    Natsuki Matsushita
    Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan
    J Neurochem 82:295-304. 2002
    ..The TH promoter appears to possess transcriptional elements at least necessary for the induction of TH expression at the early embryonic stage and its reactivation during the post-natal development...
  30. pmc Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons
    K Sawamoto
    Division of Neuroanatomy (D12, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
    Proc Natl Acad Sci U S A 98:6423-8. 2001
    ..This strategy for isolating an enriched population of DA neurons should be useful for cellular and molecular studies of these neurons and for clinical applications in the treatment of Parkinson's disease...
  31. ncbi Expression of neuronal markers suggests heterogeneity of chick sympathoadrenal cells prior to invasion of the adrenal anlagen
    Uwe Ernsberger
    Department of Neuroanatomy, Interdisciplinary Center for Neurosciences IZN, University of Heidelberg, INF 307, 69120 Heidelberg, Germany
    Cell Tissue Res 319:1-13. 2005
    ....
  32. ncbi The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors
    T Beck
    Department of Biochemistry, Biozentrum, University of Basel, Switzerland
    Nature 402:689-92. 1999
    ..Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm...
  33. ncbi Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb
    Minoree Kohwi
    Department of Neurological Surgery, Program in Developmental and Stem Cell Biology, University of California, San Francisco, California 94143, USA
    J Neurosci 25:6997-7003. 2005
    ..Our data show that SVZ neuroblasts are heterogeneous and that Pax6 is required in a cell-autonomous manner for the production of cells in the dopaminergic lineage...
  34. ncbi Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
    C Y Peng
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 277:1501-5. 1997
    ..These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells...
  35. ncbi 14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac. Platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3 zeta
    Katarzyna Bialkowska
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 278:33342-50. 2003
    ..Thus, introduction of the 14-3-3 zeta binding domain of GP Ibalpha into target cells might provide a method for regulating integrin-induced pathways in a variety of pathological conditions...
  36. pmc Induction of striatal pre- and postsynaptic damage by methamphetamine requires the dopamine receptors
    Wenjing Xu
    Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA
    Synapse 58:110-21. 2005
    ..Moreover, since blockade of either receptor subtype protected from METH, the activity of both DA receptor subtypes is required for the induction of toxicity by METH in the striatum...
  37. ncbi Role of oxidative stress in paraquat-induced dopaminergic cell degeneration
    Alison L McCormack
    The Parkinson s Institute, Sunnyvale, CA 94089, USA
    J Neurochem 93:1030-7. 2005
    ..Thus, paraquat exposure yields a model that emphasizes the susceptibility of dopaminergic neurons to oxidative damage...
  38. ncbi Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease
    Gaëlle Bouchez
    INSERM U930, Laboratory Biophysique médicale and pharmaceutique, UFR Pharmacie, 31 Avenue Monge, Tours, France
    Neurochem Int 52:1332-42. 2008
    ..This cellular approach might be a restorative therapy in Parkinson's disease...
  39. ncbi Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain
    Lachlan H Thompson
    Department of Experimental Medical Science, Lund University, Lund, Sweden
    Eur J Neurosci 30:625-38. 2009
    ..Results from testing of amphetamine-induced rotational behaviour suggest, moreover, that dopamine neurons implanted into the substantia nigra are also capable of integrating into the host circuitry at the functional level...
  40. ncbi Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells
    Shun Yu
    Department of Neurobiology and the Sino Japan Joint Laboratory on Neurodegenerative Diseases, Beijing Institute of Geriatrics, Xuanwu Hospital of the Capital University of Medical Sciences, 45 Changchun Street, Beijing 100053, China
    Neurosci Lett 367:34-9. 2004
    ..No apparent cell injury or death was observed. These results suggest that an abnormal expression of alpha-Syn may inhibit TH synthesis in dopaminergic cells...
  41. pmc Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity
    Hiroshi Kawasaki
    Department of Medical Embryology and Neurobiology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Proc Natl Acad Sci U S A 99:1580-5. 2002
    ..The SDIA method provides an unlimited source of primate cells for the study of pathogenesis, drug development, and transplantation in degenerative diseases such as Parkinson's disease and retinitis pigmentosa...
  42. ncbi Evolution of the 14-3-3 protein family: does the large number of isoforms in multicellular organisms reflect functional specificity?
    M Rosenquist
    Department of Plant Biochemistry, Lund University, P O Box 117, SE 221 00 Lund, Sweden
    J Mol Evol 51:446-58. 2000
    ..Thus, our data suggest that one reason for the large number of isoforms found in multicellular organisms is isoform-specific functions...
  43. ncbi Regulation of tyrosine hydroxylase by stress-activated protein kinases
    Karen Toska
    Department of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway
    J Neurochem 83:775-83. 2002
    ..These studies provide new insights into the possible roles of stress-activated protein kinases in the regulation of catecholamine biosynthesis...
  44. pmc DNA damage and replication checkpoints in fission yeast require nuclear exclusion of the Cdc25 phosphatase via 14-3-3 binding
    Y Zeng
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    Mol Cell Biol 19:7410-9. 1999
    ..These results indicate that 14-3-3 binding contributes to the nuclear exclusion of Cdc25 and that the nuclear exclusion of Cdc25 is required for a normal checkpoint response to both damaged and unreplicated DNA...
  45. ncbi Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells
    S Finotto
    Neuroanatomy, University of Heidelberg, D 69120 Heidelberg, Germany
    Development 126:2935-44. 1999
    ..These data strongly suggest that the dogma of an essential role of glucocorticoid signalling for the development of chromaffin cells must be abandoned...
  46. ncbi Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons
    Valerie M Tatard
    INSERM Unit 646, Ingenierie de la Vectorisation Particulaire, 10, rue André Bocquel, 49100 Angers, Centre Hospitalier Universitaire d Angers, 4 rue Larrey, France
    Bone 40:360-73. 2007
    ..MIAMI cells from young and old individuals represent autologous human cell populations for the treatment of disorders of the skeletal and nervous systems and for applications in cell therapy and reparative medicine approaches...
  47. ncbi Selective blockade of mGlu5 metabotropic glutamate receptors is protective against methamphetamine neurotoxicity
    Giuseppe Battaglia
    Instituto Neuromed Mediterraneo, Pozzilli Isernia 86077, Italy
    J Neurosci 22:2135-41. 2002
    ..We conclude that endogenous activation of mGlu5 receptors enables the development of MA neurotoxicity and that mGlu5 receptor antagonists are neuroprotective without interfering with the primary mechanism of action of MA...
  48. ncbi Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesis
    Larisa Bobrovskaya
    School of Biomedical Sciences and Hunter Medical Research Institute, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia
    J Neurochem 100:479-89. 2007
    ..Sustained phosphorylation of TH may be a selective target for drugs or pathology in neurons that contain TH and synthesize dopamine, noradrenaline or adrenaline...
  49. ncbi 14-3-3 proteins mediate an essential anti-apoptotic signal
    S C Masters
    Graduate Program in Molecular and Systems Pharmacology and the Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 276:45193-200. 2001
    ..Inhibition of 14-3-3 may represent a useful therapeutic target for treatment of cancer and other diseases involving inappropriate cell survival...
  50. ncbi 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression
    H Hermeking
    Johns Hopkins Oncology Center, Baltimore, Maryland, USA
    Mol Cell 1:3-11. 1997
    ..As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, these results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53...
  51. ncbi A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets
    Mahmoud M Iravani
    Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King s College, London SE1 1UL, UK
    Eur J Neurosci 21:841-54. 2005
    ..In addition, these partially lesioned animals did not respond to acute treatment with L-DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD...
  52. pmc Mutant alpha-synuclein overexpression mediates early proinflammatory activity
    Xiaomin Su
    Center for Aging and Developmental Biology, Aab Institute for Biomedical Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    Neurotox Res 16:238-54. 2009
    ..Together, these data demonstrate that mutated alpha-synuclein mediates a proinflammatory response in microglia and this activity may participate in PD pathogenesis...
  53. pmc The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity
    David M Thomas
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA
    J Neurochem 105:605-16. 2008
    ..Our results also suggest that reactants derived from METH-induced oxidation of released DA may serve as neuronal signals that lead to microglial activation early in the neurotoxic process associated with METH...
  54. ncbi Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone
    Sarah A Baker
    Kentucky Spinal Cord Injury Research Center, University of Louisville, 511 S Floyd Street, MDR Room 616, Louisville, KY 40292, USA
    Eur J Neurosci 20:575-9. 2004
    ..This identifies dopamine as one of the few known endogenous regulators of adult neurogenesis with implications for the potential use of endogenous neural precursors in cell replacement strategies for Parkinson's disease...
  55. ncbi Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease
    E Bezard
    Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom
    J Neurosci 21:6853-61. 2001
    ....
  56. ncbi Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro
    S M Meusburger
    Department of Physiology and Pharmacology, University of Queensland, St Lucia, QLD 4072, Australia
    Neuroscience 108:331-40. 2001
    ....
  57. ncbi GDNF applied to the MPTP-lesioned nigrostriatal system requires TGF-beta for its neuroprotective action
    Andreas Schober
    IZN, Department of Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, D 69120 Heidelberg, Germany
    Neurobiol Dis 25:378-91. 2007
    ..We conclude that striatal TGF-beta may be essential for permitting exogenous GDNF to act as a neuroprotective factor...
  58. ncbi The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration
    Massimo M Santoro
    Department of Medical Sciences, University of Piemonte Orientale A Avogadro, 28100, Novara, Italy
    Dev Cell 5:257-71. 2003
    ....
  59. ncbi Tyrosine hydroxylase phosphorylation: regulation and consequences
    Peter R Dunkley
    School of Biomedical Sciences, The University of Newcastle, Callaghan, New South Wales, Australia
    J Neurochem 91:1025-43. 2004
    ..Hierarchical phosphorylation depends on the state of the substrate providing a novel form of control of tyrosine hydroxylase activation...
  60. pmc ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ
    J W Haycock
    Department of Biochemistry, Louisiana State University Medical Center, New Orleans 70119
    Proc Natl Acad Sci U S A 89:2365-9. 1992
    ....
  61. ncbi Regulation of CDC25B phosphatases subcellular localization
    N Davezac
    LBCMCP CNRS UMR5088, Universite Paul Sabatier, Toulouse, France
    Oncogene 19:2179-85. 2000
    ..The subcellular localization of CDC25B is therefore dependent on the combined effects of a nuclear localization signal, a nuclear export signal and on the interaction with 14-3-3 proteins...
  62. ncbi The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum)
    E Rink
    Brain Research Institute, University of Bremen, P O Box 33 04 40, D 28334, Bremen, Germany
    Brain Res 889:316-30. 2001
    ..They are interpreted as the teleostean dopaminergic system ascending to the striatum, since previous work [16] established that no noradrenergic neurons exist in the forebrain of the adult zebrafish...
  63. pmc RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals
    Sebastian Kowsky
    Department of Neurodegeneration and Restorative Research, Centers of Molecular Physiology of the Brain and Neurological Medicine, University of Goettingen, Waldweg 33, D 37073 Goettingen, Germany
    Proc Natl Acad Sci U S A 104:20049-54. 2007
    ..We therefore conclude that RET signaling has no influence on the survival of dopaminergic neurons in the MPTP model of Parkinson's disease but rather facilitates the regeneration of dopaminergic axon terminals...
  64. ncbi Parkinson's disease--redox mechanisms
    J D Adams
    USC School of Pharmacy, 1985 Zonal Avenue, PSC 508, Los Angeles, CA 90089 9121, USA
    Curr Med Chem 8:809-14. 2001
    ..The redox mechanisms of oxygen radical formation by MPTP, tyrosine hydroxylase, monoamine oxidase and aldehyde dehydrogenase will be discussed. Possible clinical applications of these mechanisms will be briefly presented...
  65. ncbi Subcellular localization of 14-3-3 proteins in Toxoplasma gondii tachyzoites and evidence for a lipid raft-associated form
    Olga Assossou
    Laboratoire de Parasitologie, Mycologie Medicale et Pathologie Exotique, Equipe d accueil EA 3087 Faculté de Médecine, Universite Claude Bernard, 8 avenue Rockefeller, 69373, Lyon, Cedex 08, France
    FEMS Microbiol Lett 224:161-8. 2003
    ..Two 14-3-3 isoforms were detected. The major one was mainly cytoplasmic and to a lesser extent membrane-associated, whereas the minor isoform was associated with the detergent-resistant lipid rafts...
  66. ncbi Immunohistochemical characterisation of pelvic autonomic ganglia in male mice
    Yewlan Wanigasekara
    Prince of Wales Medical Research Institute, University of New South Wales, Sydney, Australia
    Cell Tissue Res 311:175-85. 2003
    ..These studies provide the framework for future investigations on neural regulation of urogenital function, particularly in transgenic and knockout models...
  67. pmc Interaction of a plant 14-3-3 protein with the signal peptide of a thylakoid-targeted chloroplast precursor protein and the presence of 14-3-3 isoforms in the chloroplast stroma
    P C Sehnke
    Program in Plant Molecular and Cellular Biology, Department of Horticultural Sciences, University of Florida, Gainesville, Florida 32611, USA
    Plant Physiol 122:235-42. 2000
    ..These isoforms represent two distinct phylogenetic 14-3-3 groupings. These data suggest a novel interorganellar role for these phylogenetically distinct 14-3-3 proteins...
  68. ncbi Phylogenetic investigation of Dogiel's pericellular nests and Cajal's initial glomeruli in the dorsal root ganglion
    Seiji Matsuda
    Department of Anatomy and Embryology, Ehime University School of Medicine, Toon, Ehime 791 0295, Japan
    J Comp Neurol 491:234-45. 2005
    ..Such TH-positive PCNs disappear after sympathectomy. These results suggest that the PCNs are made up of autonomic nerve fibers...
  69. ncbi Differential expression of the B'beta regulatory subunit of protein phosphatase 2A modulates tyrosine hydroxylase phosphorylation and catecholamine synthesis
    Amit Saraf
    Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
    J Biol Chem 282:573-80. 2007
    ..In summary, we show that B'beta recruits PP2A to modulate TH activity in a tissue- and cell compartment specific fashion...
  70. ncbi The human tyrosine hydroxylase gene promoter
    Mark A Kessler
    Department of Neurology and Farber Institute for the Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Brain Res Mol Brain Res 112:8-23. 2003
    ..Within these conserved regions (CRs I-V), potential recognition sites for NR4A2 (Nurr1), HNF-3beta, HOXA4, and HOXA5 were shared across human, mouse, and rat TH promoters...
  71. ncbi Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease
    Deepinder Kaur
    Buck Institute for Age Research, Novato, CA 94945, USA
    Neuron 37:899-909. 2003
    ....
  72. ncbi Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons
    Yewlan Wanigasekara
    Prince of Wales Medical Research Institute, University of New South Wales, Randwick NSW 2031, Australia
    Eur J Neurosci 22:595-604. 2005
    ..Our results also indicate that neurotrophic signalling in parasympathetic neurons is different from that in other types of peripheral neurons...
  73. ncbi C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding
    C Y Peng
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell Growth Differ 9:197-208. 1998
    ..Taken together, these results suggest that one function of C-TAK1 may be to regulate the interactions between Cdc25C and 14-3-3 in vivo by phosphorylating Cdc25C on serine 216...
  74. ncbi Tyrosine hydroxylase immunoreactivity in the developing visual pathway of the zebrafish
    F J Arenzana
    Dpto de Biología Celular y Patología, Instituto de Neurociencias de Castilla y Leon, Universidad de Salamanca Facultad de Medicina, Campus Miguel de Unamuno, Avda Alfonso X El Sabio, 1, E 37007, Salamanca, Spain
    Anat Embryol (Berl) 211:323-34. 2006
    ..The existence of immunolabeled neuropile in the zebrafish retinorecipient strata could be related to the turnover of retinotectal projections...
  75. ncbi GDNF family receptors in the embryonic and postnatal rat heart and reduced cholinergic innervation in mice hearts lacking ret or GFRalpha2
    J O Hiltunen
    Program of Molecular Neurobiology, Institute of Biotechnology, University of Helsinki, Finland
    Dev Dyn 219:28-39. 2000
    ..These findings indicate that GFRalpha2/Ret signaling is required for normal cholinergic innervation of heart...
  76. pmc The phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease
    Oleg S Gorbatyuk
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 105:763-8. 2008
    ..This suggests possible new therapeutic targets for Parkinson Disease...
  77. pmc 14-3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: localization of dopamine regulatory proteins to mitochondria
    Jian Wang
    Departments of Neurology and Pharmacology and Chemical Biology
    J Biol Chem 284:14011-9. 2009
    ....
  78. ncbi Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra
    Fumiaki Mori
    Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, Japan
    J Neuropathol Exp Neurol 65:808-15. 2006
    ..Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD...
  79. pmc The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?
    Elyssa B Margolis
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA
    J Physiol 577:907-24. 2006
    ..We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable...
  80. ncbi Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens
    Julie Bakker
    Center for Cellular and Molecular Neurobiology, University of Liege, Avenue de l Hopital 1, B36, 4000 Liege, Belgium
    Nat Neurosci 9:220-6. 2006
    ..These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens...
  81. ncbi Phosphorylation of Ser19 increases both Ser40 phosphorylation and enzyme activity of tyrosine hydroxylase in intact cells
    Larisa Bobrovskaya
    The School of Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, The University of Newcastle, Callaghan, Australia
    J Neurochem 90:857-64. 2004
    ..These data provide the first evidence that the phosphorylation of Ser19 can potentiate the phosphorylation of Ser40 and subsequent activation of tyrosine hydroxylase in intact cells...
  82. ncbi Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat
    Alison L McCormack
    The Parkinson s Institute, Sunnyvale, California 94089, USA
    Neurobiol Dis 10:119-27. 2002
    ....
  83. ncbi A novel rap1/B-Raf/14-3-3 theta protein complex is formed in vivo during the morphogenetic differentiation of postmeiotic male germ cells
    G Berruti
    Department of Biology, Milan University, Italy
    Exp Cell Res 257:172-9. 2000
    ....
  84. ncbi GFRalpha-1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area
    A Sarabi
    Cellular Neurophysiology, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA
    J Comp Neurol 441:106-17. 2001
    ....
  85. ncbi Leonardo, a Drosophila 14-3-3 protein involved in learning, regulates presynaptic function
    K Broadie
    Department of Biology, University of Utah, Salt Lake City 84112, USA
    Neuron 19:391-402. 1997
    ..These results suggest that Leonardo plays a role in the regulation of synaptic vesicle dynamics, a function which may underlie synaptic modulation properties enabling learning...
  86. ncbi Dopamine is not required for the hyperlocomotor response to NMDA receptor antagonists
    Elena H Chartoff
    Department of Psychiatry, Harvard Medical School, McLean Hospital Belmont, MA, USA
    Neuropsychopharmacology 30:1324-33. 2005
    ..These results suggest that glutamate, rather than dopamine, is required for the locomotor and molecular effects of NMDA receptor antagonists, but that glutamate and dopamine can act cooperatively...
  87. pmc Involvement of 14-3-3 proteins in nuclear localization of telomerase
    H Seimiya
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
    EMBO J 19:2652-61. 2000
    ..14-3-3 binding was not required for telomerase activity either in vitro or in cell extracts. These observations suggest that 14-3-3 enhances nuclear localization of TERT by inhibiting the CRM1 binding to the TERT NES-like motif...
  88. ncbi Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)
    J Zha
    Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 87:619-28. 1996
    ..The rapid phosphorylation of BAD following IL-3 connects a proximal survival signal with the BCL-2 family, modulating this checkpoint for apoptosis...
  89. ncbi Binding of 14-3-3beta regulates the kinase activity and subcellular localization of testicular protein kinase 1
    J Y Toshima
    Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai 980 8578, Japan
    J Biol Chem 276:43471-81. 2001
    ..We propose that 14-3-3beta plays important roles in regulating the kinase activity of TESK1 and localizing TESK1 to cell adhesion sites following integrin stimulation...
  90. pmc Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease
    Deniz Kirik
    Wallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, BMC A11, 221 84 Lund, Sweden
    Proc Natl Acad Sci U S A 100:2884-9. 2003
    ..This model offers new opportunities for the study of pathogenetic mechanisms and exploration of new therapeutic targets of particular relevance to human PD...
  91. ncbi The role of dopamine in learning, memory, and performance of a water escape task
    Victor H Denenberg
    Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195 7370, USA
    Behav Brain Res 148:73-8. 2004
    ....
  92. ncbi BDNF and CNTF regulate cholinergic properties of sympathetic neurons through independent mechanisms
    John D Slonimsky
    Department of Biology, Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA
    Mol Cell Neurosci 23:648-60. 2003
    ..The results of this study indicate that BDNF and CNTF, acting through independent pathways, modulate NE and ACh cotransmission to regulate the level of sympathetic excitation or inhibition of cardiac myocytes...
  93. ncbi Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum
    John W Haycock
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center, New Orleans 70119, USA
    J Neurochem 87:574-85. 2003
    ..This suggests that declines in DA-related function during adulthood and senescence may be explained by losses in DA per se as opposed to DAergic neuropil...
  94. ncbi Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture
    Thomas C Schulz
    BresaGen Inc, 111 Riverbend Rd, Athens, Georgia, 30605, USA
    Stem Cells 22:1218-38. 2004
    ..This work suggests that hESCs can differentiate in simple serum-free suspension cultures to produce the large number of cells required for transplantation studies...
  95. ncbi Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease
    Lingling Lu
    Beijing Institute for Neuroscience, The Beijing Center of Neural Regeneration and Repairing, Capital University of Medical Sciences, 10 You anMen Wai Xitoutiao, Beijing 100054, P R China
    Brain Res Brain Res Protoc 15:46-51. 2005
    ..05). All the data demonstrated that MSCs could readily be genetically engineered. Therefore, MSCs could be useful gene delivery vehicles of gene therapy for Parkinson's disease...
  96. ncbi Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease?
    Yaping Chu
    Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA
    Neurobiol Dis 25:134-49. 2007
    ..We further hypothesize that preventing the age-related accumulation of non-aggregated alpha-synuclein might be a simple and potent therapeutic target for patients with PD...
  97. ncbi Early loss of dopaminergic terminals in striosomes after MDMA administration to mice
    Noelia Granado
    Instituto Cajal, Consejo Superior de Investigaciones Cientificas, CSIC, Madrid 28002, Spain
    Synapse 62:80-4. 2008
    ....
  98. ncbi Phosphatidylinositol 3-kinase signaling inhibits DAF-16 DNA binding and function via 14-3-3-dependent and 14-3-3-independent pathways
    C M Cahill
    Diabetes Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 276:13402-10. 2001
    ..Thus, our results demonstrate at least two mechanisms, one 14-3-3-dependent and the other 14-3-3-independent, whereby PI 3-kinase signaling regulates DAF-16 DNA binding and transcription function...
  99. ncbi Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo
    J Holzschuh
    Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D 79104, Freiburg, Germany
    Mech Dev 101:237-43. 2001
    ..Neurons expressing th but not dat are adrenergic or noradrenergic, and are found in the locus coeruleus, the medulla, the likely analog of the carotid body, and precursors of the enteric and sympathetic nervous system...
  100. ncbi 14-3-3 proteins: key regulators of cell division, signalling and apoptosis
    M J van Hemert
    Section Yeast Genetics, Institute of Molecular Plant Sciences, Leiden University, The Netherlands
    Bioessays 23:936-46. 2001
    ..This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/Suppmat/23/v23_10.936...
  101. ncbi The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease
    Amjad Abuirmeileh
    Department of Pharmacology, The School of Pharmacy, 29 39 Brunswick Square, London, UK
    Eur J Neurosci 26:417-23. 2007
    ..The apparent ability of UCN to arrest the progression of or even reverse nigral lesions once established suggests that pharmacological manipulation of this system could have substantial therapeutic utility...

Research Grants78

  1. ADRENAL CATECHOLAMINE SECRETION
    ROBERT PERLMAN; Fiscal Year: 1980
    ..Finally, we will investigate the extent to which catecholamine secretion and catecholamine synthesis are co-ordinately regulated...
  2. Molecular Neurobiology of Drug Abuse
    DONALD KUHN; Fiscal Year: 2006
    ..Kuhn will remain extensively engaged in scientific mentoring activities. ..
  3. PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
    DONALD KUHN; Fiscal Year: 2002
    ....
  4. Hormonal Factors and Recruitment of Neurons into the Stress Response Circuitry
    Wendi S Neckameyer; Fiscal Year: 2010
    ..This will provide a unique and innovative approach to modeling the development and organization of the stress circuitry in mammals. ..
  5. MICROARRAY ANALYSIS OF HUMAN COCAINE ADDICTS
    DONALD KUHN; Fiscal Year: 2002
    ..Microarray-based scanning of the human genome has the potential to establish those genes or gene clusters that define the addictive phenotype, leading the way to proteomic-based studies of the bases of addiction. ..
  6. Methamphetamine Neurotoxicity and Microglial Activation
    DONALD KUHN; Fiscal Year: 2009
    ..A better understanding of the mechanisms by which METH causes persistent damage to the DA neuronal system could lead to more targeted therapies and would open newer lines of investigation into this and other neurotoxic drugs of abuse. ..
  7. NEUROSCIENCE TRAINING IN DRUG ABUSE
    DONALD KUHN; Fiscal Year: 2004
    ..abstract_text> ..
  8. MOLECULAR ANALYSIS OF THE DROSOPHILA GABA TRANSPORTERS
    Wendi Neckameyer; Fiscal Year: 2001
    ....
  9. MOLECULAR BIOLOGY OF NOREPINEPHRINE BIOSYNTHESIS
    Esther Sabban; Fiscal Year: 2006
    ..These findings will contribute to the development of new strategies to prevent the harmful maladaptive changes in catecholamine neurotransmission, while enhancing its beneficial adaptive aspects ..
  10. Sympathetic Ganglia: New Target for ACTH with Stress
    Esther Sabban; Fiscal Year: 2008
    ..abstract_text> ..
  11. ENERGY METABOLISM, DOPAMINE NEURONS AND NEUROTOXICITY
    Gail Zeevalk; Fiscal Year: 2008
    ..The studies will have relevance to neurodegenerative conditions or pathophysiological situations in which metabolism is compromised. ..
  12. Developmental Affects of Ritalin on Brain
    TERESA MILNER; Fiscal Year: 2004
    ..Determining how therapeutic dosage regimens effect these transmitter systems is critical in understanding the safety of long-term therapeutic doses of MPH administered to children and adolescents with ADHD and other related disorders. ..
  13. TH and GTPCHI gene therapy for Parkinson's disease
    Jeffrey H Kordower; Fiscal Year: 2010
    ..These studies will determine the safety and efficacy of gene delivery of LDOPA and determine whether this approach is appropriate for clinical trials. ..
  14. HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
    John Haycock; Fiscal Year: 2003
    ..age-matched, sudden-death control subjects having no Axis 1 mental disorder. Parallel, collaborative studies of major depressives will provide comparison groups and allow identification of potential disease-specific differences. ..
  15. DYSKINESIAS IN LENTI-GDNF TREATED PARKINSONIAN MONKEYS
    Jeffrey Kordower; Fiscal Year: 2006
    ..This application will determine whether potent dopaminergic gene therapies influence dyskinesias in the best animal model of PD. ..
  16. MESOLIMBIC DOPAMINE D3 RECEPTOR AND PARKINSON'S DISEASE
    Jeffrey Joyce; Fiscal Year: 2002
    ..This will further elucidate the pathology of DAergic substrates of specific clinical symptoms in PD and provide a broader basis for developing effective treatment strategies based on specific DA receptors. ..
  17. CELLULAR REGULATION OF TYROSINE HYDROXYLASE
    John Haycock; Fiscal Year: 2001
    ..The effects of haloperidol on Ser19, Ser3l, and Ser4O phosphorylation will be studied by immunohistochemical and blot immunolabeling procedures using site- and phosphorylation state-specific antibodies. ..
  18. DOPAMINE AND RETINAL ADAPTATION
    Paul Witkovsky; Fiscal Year: 2001
    ....
  19. NCRR Shared Instrumentation Grant (SIG) Program
    Michael Yaffe; Fiscal Year: 2005
    ..abstract_text> ..
  20. Neurotoxicology of dietary iron/manganese interactions
    Keith Erikson; Fiscal Year: 2005
    ..If successful, these studies will lay the foundation for the development of a pharmacological therapy aimed at the prevention of manganese-accumulation in vulnerable populations. ..
  21. 2004 Growth Factor Signalling Gordon Conference
    Michael Yaffe; Fiscal Year: 2008
    ..abstract_text> ..
  22. Does Nasal Stimulation Activate Presympathetic Neurons?
    Paul McCulloch; Fiscal Year: 2005
    ..As such, this research has implications for understanding the etiology of neurogenic hypertension. ..
  23. Subcortical Estrogen Effect on The Hippocampus
    Csaba Leranth; Fiscal Year: 2005
    ..cholinergic and GABAergic septo-hippocampal neurons involved in mediating estrogenic effect to the hippocampus? and (d) Do SUM neurons mediate estrogenic effect to the hippocampus directly or indirectly, via the MSDB? ..
  24. High-Throughput Assay Design:Polo Kinase Inhibitors(RMI)
    Michael Yaffe; Fiscal Year: 2004
    ..The development of these assays should allow rapid screening of small molecule Polo kinase inhibitors that will function as novel anti-cancer agents. ..
  25. Parkinsonian mouse model: impaired respiratory enzymes
    Lars Olson; Fiscal Year: 2005
    ..2. To determine if respiratory chain dysfunction in DA neurons will induce a PD like phenotype and validate this approach as a new and unique model of Parkinson's Disease. ..
  26. Identification of Molecular Pathways in Cancer Biology
    Michael Yaffe; Fiscal Year: 2005
    ..abstract_text> ..
  27. Prenatal Endotoxin as a Model of Parkinson's Disease
    Zaodung Ling; Fiscal Year: 2006
    ..abstract_text> ..
  28. ALTERED ETHANOL EFFECTS ON OSTEOCALCIN NULL MUTANT MICE
    Patricia Patterson Buckendahl; Fiscal Year: 2006
    ....
  29. Negative Effects of Bisphenol A on the Monkey CNS
    Csaba Leranth; Fiscal Year: 2008
    ..Therefore, we propose to reveal the effect of BPA on estrogen-induced spine synapse formation in the brain of non-human primates, which will provide more relevance to human health. [unreadable] [unreadable] [unreadable]..
  30. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  31. Molecular & Behavioral Effects of Low Level Mn Exposure
    TOMAS GUILARTE; Fiscal Year: 2008
    ..The knowledge gained will help set future public health policies and guidelines to limit Mn exposures in occupational settings and to the general population. ..
  32. SPINAL CORD REPAIR WITH HUMAN UMBILICAL CORD BLOOD CELLS
    Samuel Saporta; Fiscal Year: 2003
    ..abstract_text> ..
  33. Fetal & Adolescent Nicotine Effects on CNS 5HT Systems
    Theodore Slotkin; Fiscal Year: 2003
    ..abstract_text> ..
  34. Estrogenic Effect on Hippocampal Theta Rhythm and Memory
    Csaba Leranth; Fiscal Year: 2004
    ....
  35. MECHANISMS OF CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY
    Theodore Slotkin; Fiscal Year: 2004
    ..Molecular mechanisms of developmental neurotoxicity can be determined and linked to eventual alterations in behavioral performance. ..
  36. DRUGS AND DEVELOPMENT OF THE ADRENERGIC NERVOUS SYSTEM
    Theodore Slotkin; Fiscal Year: 2003
    ....
  37. The link between lipid peroxidation and manganese induced glutathione depletion
    Keith Erikson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  38. AMYLOIDOGENIC EFFECTS OF CHOLINERGIC DENERVATION
    Thomas Beach; Fiscal Year: 2002
    ..This could lead to impaired cerebral vasoregulation and increased susceptibility to ischemia, further compromising cortical function in AD. ..
  39. Trigeminal Autonomic Interactions
    Paul McCulloch; Fiscal Year: 2002
    ..Having a better understanding of brainstem cardiorespiratory integration might provide a neurological basis for the etiology of SIDS. ..
  40. Effects of Stress on Pathology of Parkinson's Disease
    GERLINDE METZ; Fiscal Year: 2004
    ..These approaches will provide the opportunity to understand factors involved in the pathology of PD and to develop novel therapeutic strategies for neurodegenerative motor disorders. ..
  41. Selective Prenatal Dopamine Damage in Non Human Primates
    John Elsworth; Fiscal Year: 2003
    ..Thus, the proposed work may lead ultimately to an animal model for one or more pediatric brain disorders. ..
  42. ROD NEURODEGENERATIVE AND PROTECTIVE GENES
    Baerbel Rohrer; Fiscal Year: 2005
    ..We expect to isolate common downstream target genes that are activated both during degeneration and neuroprotection. ..
  43. Non-Viral Gene Targeting to the Brain
    William Pardridge; Fiscal Year: 2008
    ..abstract_text> ..
  44. Vascular determinants of sympathetic innervation
    DEBORAH DAMON; Fiscal Year: 2008
    ....
  45. Hindbrain integration of adiposity and satiety signals
    Diana Williams; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  46. MICROARRAY ANALYSIS OF RETINAL DEGENERATION IN MICE
    Caroline Zeiss; Fiscal Year: 2007
    ..Colin Barnstable, Professor of Neurobiology and Ophthalmology, who is an internationally recognized molecular biologist using mouse models of retinal development and degeneration. ..
  47. Role of inflammation in manganese neurotoxicity: molecular mechanisms
    Nikolay M Filipov; Fiscal Year: 2010
    ..Namely, individuals with underlying inflammatory response at the time of exposure to Mn or individuals with increased body burdens of Mn, who are exposed to strong inflammatory stimuli. ..
  48. Dopamine Function in TBI--Therapeutic Intervention
    Amy Wagner; Fiscal Year: 2005
    ..The Departments of Physical Medicine and Rehabilitation, Neurosurgery, Anesthesia/Critical Care Medicine, and Safar Center for Resuscitation Research provide the environment for this study of experimental and clinical brain injury. ..
  49. NR3 Expression in Human Brain
    Helena Mueller; Fiscal Year: 2003
    ..abstract_text> ..
  50. AGING AND DOPAMINE GRAFTS IN PARKINSONIAN MONKEYS
    Timothy Collier; Fiscal Year: 2003
    ....
  51. Basement Membrane Topography and Urothelial Function
    Christopher Murphy; Fiscal Year: 2004
    ..The proposed studies will generate information pertinent to tissue engineering and development of prosthetic devices for use in the urinary tract, as well as providing data to initiate mechanistic studies. ..
  52. FUNCTIONAL PROBES FOR BRAIN HISTAMINE H1 RECEPTORS
    Raymond Booth; Fiscal Year: 2007
    ..As most untoward H1-mediated effects proceed via IP signaling, PATs that selectively enhance H1 cAMP signaling will provide a mechanistic basis for exploiting brain H1 receptors as drug targets in neuropsychiatric diseases. ..
  53. DOPAMINERGIC SIGNALING IN NEUROLOGICAL DISORDERS
    Anita Sidhu; Fiscal Year: 2005
    ....
  54. Antisense imaging of brain gene expression in vivo
    William Pardridge; Fiscal Year: 2005
    ..This technology could be extended to humans and to other organs. At present, there is no parallel technology that enables the non-invasive in vivo imaging of "any gene in any person," which is the goal of this work. ..
  55. Angiotensin Receptors in Central Osmonsensitivity
    Mariana Morris; Fiscal Year: 2005
    ..abstract_text> ..
  56. Sympathetic Modulation of the Immune System in Aging
    Denise Bellinger; Fiscal Year: 2005
    ..Specific Aim 3 explores possible mechanisms responsible for the age-related differences in sympathetic innervation of secondary lymphoid organs from these two rat strains. ..
  57. Immune Responsiveness, APOE/Gender in Neurodegeneration
    Carol Colton; Fiscal Year: 2008
    ..Thus, we will examine the role of hormones in the regulation of microglial and peritoneal macrophage immune activation in mice expressing only human apoE3 protein or expressing only human apoE4 protein. ..
  58. Gene Therapy, Neural Grafts & Parkinson's Disease
    DAVID YUREK; Fiscal Year: 2005
    ..These studies will also determine if combinations of viral vectors expressing different neurotrophic factors can be used to improve the therapeutic effects of dopamine grafts. ..
  59. New Clinical Approaches to Creutzfeldt-Jakob Disease
    Michael Geschwind; Fiscal Year: 2007
    ..Geschwind's training in behavioral neurology and neuroscience, thereby helping him to design and implement future clinical treatment studies for human prion disease and other dementias. ..
  60. Mechanisms of Psychosocial Influences on Prostate Cancer
    Denise Bellinger; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  61. Iron Acquisition Mechanisms in Oligodendrocytes
    JAMES ROBERT CONNOR; Fiscal Year: 2010
    ..abstract_text> ..
  62. Translocation and Function of Nuclear Ferritin
    James Connor; Fiscal Year: 2004
    ..abstract_text> ..
  63. DOPAMINERGIC NEUROTOXINS AND AGING
    PATRICIA SONSALLA; Fiscal Year: 2004
    ..These studies will provide novel and relevant Information as to the contribution of VMAT2-containing vesicles in neuroprotection as well as in neurodegeneration under conditions of a metabolic stress. ..
  64. ALPHA-1 ADRENERGIC SYSTEM IN ACTIVITY AND DEPRESSION
    Eric A Stone; Fiscal Year: 2010
    ..The research will likely identify the EPI/alpha-1 system as a new and important target for antidepressant and antistress medications ..
  65. Adenosine, Glutamate and Neurodegeneration
    PATRICIA SONSALLA; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  66. DEVELOPING AND IMPROVING INSTITUTIONAL ANIMAL RESOURCES
    PATRICIA SONSALLA; Fiscal Year: 2005
    ..abstract_text> ..
  67. DOPAMINERGIC FUNCTION IN RESTLESS LEGS SYNDROME
    Christopher Earley; Fiscal Year: 2001
    ..The authors would also explore relationships between iron and CSF measures of dopaminergic activities, which could provide the basis for entirely new research and treatment approaches to RLS. ..
  68. Non-invasive self administration methodology for mice
    Jay Hirsh; Fiscal Year: 2004
    ..These mice will be made available to the scientific community even before they are fully characterized. We will obtain these lines when available as homozygotes and test them in our paradigm. ..
  69. Enteric Neuronal Survival in Diabetes
    Shanthi Srinivasan; Fiscal Year: 2008
    ....
  70. Genetic Manipulation of Phasic Dopaminergic Activity
    Jeff Beeler; Fiscal Year: 2007
    ..A computational model formalizing a hypothesized relationship between reinforcement learning and motivation and incorporating both phasic and tonic activity will be developed. ..
  71. DEVELOPMENT OF THE GUSTATORY SYSTEM
    RICHARD NORTHCUTT; Fiscal Year: 2005
    ..To test the hypothesis that retinoic acid acts as a signal to pattern endoderm directly during gastrulation (aim 3), presumptive pharyngeal endoderm will be excised, exposed to retinoic acid, and cultured. ..
  72. DETERMINING THE GENETICS OF RESTLESS LEGS SYNDROME
    Christopher Earley; Fiscal Year: 2003
    ....
  73. Dopamine Homeostasis, Vesicles & Neurodegeneration
    PATRICIA SONSALLA; Fiscal Year: 2004
    ..Results from these studies will provide novel and relevant information as to the contribution of VMAT2 containing vesicles in neuroprotection as well as in neurodegeneration of DA neurons during metabolic stress. ..
  74. Dopamine and Iron in Restless Legs Syndrome
    Christopher Earley; Fiscal Year: 2006
    ..Using CSF and MRI measurements of iron will assess the CNS iron status. RLS severity will be based on subjective (rating scale and diary) and objective (PSG) measurements. ..
  75. Role of Nonclassical Transmitters in Cardiac Ganglia
    Donald Hoover; Fiscal Year: 2004
    ..abstract_text> ..
  76. Response to Iron Treatment for Restless Leg Syndrome
    Christopher Earley; Fiscal Year: 2004
    ..An expected finding that IV iron reduces the brain iron insufficiency and dramatically reduces the RLS symptoms strongly supports our model of RLS caused by brain iron insufficiency. ..
  77. Psychostimulant Response Pathways
    Jay Hirsh; Fiscal Year: 2006
    ..In the fourth aim, global changes in brain gene expression as a function of cocaine exposure and sensitization will be examined in order to identify new genes candidates involved in pathways modulating cocaine responses. ..