Skip to main content
SpringerLink
Log in

The role of neurotransporters in excitotoxicity, neuronal cell death, and other neurodegenerative processes

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Neurotransporters are high-affinity transport proteins located in the plasma membrane of both presynaptic nerve and glial cells that mediate the removal of neurotransmitters from the synaptic cleft or represent intracellular transport systems that concentrate neurotransmitters in synaptic vesicles. They comprise three subgroups, Na+/Cl−- or Na+/K+-dependent cell surface transporters and H+-dependent transporters associated with synaptic vesicles. The new insights into neurotransporter diversity provide the means for novel approaches of studying neurotransmitter uptake processes at the molecular level, such as substrate translocation, antagonist binding, and regulation of gene expression, intracellular trafficking, and posttranslational modification. Moreover, modeling neurotransporter-related disorders and therapeutic strategies in genetically engineered animals are now feasible research strategies. Through an improved understanding of the modulation of neurotransporter function in the brain it may be possible to identify the molecular factors underlying the etiopathogenesis and pathophysiology of neurodegenerative disorders. Due to their specificity for distinct neuronal systems neurotransporters and their genes are potential targets for novel therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ChAT :

Choline acetyltransferase

CRE :

cAMP response element

DAT :

Dopamine transporter

GABA :

γ-Aminobutyric acid

GluT :

Glutamate transporter

5-HT :

5-Hydroxytryptamine

5-HTT :

5-HT transporter

ILPR :

Insulin gene linked polymorphic region

MDMA :

3,4-Methylenedioxymethamphetamine

MPP + :

1-Methyl-4-phenylpyridine ion

MPTP :

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD :

Parkinson's disease

TBZOH :

Dihydrotetrabenazine

VAChT :

Vesicular ACh transporter

VMT :

Vesicular monoamine transporter

References

  1. Altemus M, Murphy DL, Greenberg B, Lesch KP (1996) Intact coding region of the serotonin transporter in obsessive-compulsive disorder. Am J Med Genet (in press)

  2. Andrews AM, Murphy DL (1993) 2′-NH2-MPTP in Swiss Webster mice: evidence for long-term (6-month) depletion in cortical and hippocampal serotonin and norepinephrine, differential protection by selective uptake inhibitors or clorgyline and functional changes in central serotonin transmission. J Pharmacol Exp Therap 267:1432–1439

    Google Scholar 

  3. Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (1994) Functional comparison of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 14:5559–5569

    Google Scholar 

  4. Austin MC, Bradley CC, Mann JJ, Blakely RD (1994) Expression of serotonin transporter messenger RNA in the human brain. J Neurochem 62:2362–2367

    Google Scholar 

  5. Bannon MJ, Poosch MS, Xia Y, Goebel DJ, Cassin B, Kapatos G (1992) Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age. Proc Natl Acad Sci USA 89:7095–7099

    CAS  PubMed  Google Scholar 

  6. Bannon MJ, Granneman JG, Kapatos G (1995) The dopamine transporter: potential involvement in neuropsychiatric disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology, the fourth generation of progress. Raven, New York, pp 179–188

    Google Scholar 

  7. Bejanin S, Cervini R, Mallet J, Berrard S (1994) A unique gene organization for two cholinergic markers, choline acetyltransferase and a putative vesicular transporter of acetylcholine. J Biol Chem 269:21944–21947

    PubMed  Google Scholar 

  8. Bell GI, Selby M, Rutter WJ (1982) The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature 295:31–35

    Google Scholar 

  9. Bengel D, Heils A, Petri S, Teufel A, Seemann M, Riederer P, Lesch KP (1996) Gene structure and 5′-flanking regulatory region of the murine serotonin transporter. Mol Brain Res (in press)

  10. Bennett ST, Lucassen AM, Gough SCL, Powell EE, Undlien DE, Pritchard LE, Merriman ME, Kawaguchi Y, Dronsfield MJ, Pociot F, Nerup J, Bouzekri N, Cambon-Thomsen A, Ronningen KS, Barnett AH, Bain SC, Todd JA (1995) Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nature Genet 9:284–292

    Google Scholar 

  11. Berger SP, Farrell K, Conant D, Kempner ES, Paul SM (1994) Radiation inactivation studies of the dopamine reuptake transporter protein. Mol Pharmacol 46:726–731

    Google Scholar 

  12. Berrard S, Varoqui H, Cervini R, Israel M, Mallet J, Diebler MF (1995) Coregulation of two embedded gene products, choline acetyltransferase and the vesicular acetylcholine transporter. J Neurochem 65:939–942

    Google Scholar 

  13. Blakely RD, Berson HE. Fremeau RT, Caron MC, Peek MM, Prince HK, Bradley CC (1991) Cloning and expression of functional serotonin transporter from rat brain. Nature 354:66–70

    Google Scholar 

  14. Blakely R, De Felice LJ, Hartzell HC (1994) Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 196:263–281

    Google Scholar 

  15. Boja JW, Vaughan R, Patel A, Shaya EK, Kuhar MJ (1994) The dopamine transporter. In: Niznik HB (ed) Dopamine receptors and transporters. Dekker, New York, pp 611–644

    Google Scholar 

  16. Borden LA, Smith KE, Hartig PR, Branchek TA, Weinshank RI (1992) Molecular heterogeneity of the γ-aminobutyric acid (GABA) transport system. J Biol Chem 267:21096–21104

    Google Scholar 

  17. Brücke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine H, Podreka I (1993) SPECT imaging of dopamine and serotonin transporters with (I-123) beta-CIT binding kinetics in the human brain. J Neural Transm 94:137–146

    PubMed  Google Scholar 

  18. Byerley W, Coon H, Hoff M, Holik J, Waldo M, Freedman R, Caron MG, Giros B (1993) Human dopamine transporter gene not linked to schizophrenia in multigenerational pedigrees. Hum Hered 43:319–322

    Google Scholar 

  19. Chen HT, Clark M, Goldman D (1992) Quantitative autoradiography of 3H-paroxetine binding sites in rat brain. J Pharmacol Toxicol Methods 27:209–216

    Google Scholar 

  20. Conradt M, Stoffel W (1995) Functional analysis of the high affinity, Na(+)-dependent glutamate transporter GLAST-1 by site-directed mutagenesis. J Biol Chem 270:25207–25212

    Google Scholar 

  21. Cool DR, Leibach FH, Bhalla VK, Mahesh V, Ganapathy V (1991) Expression and cyclic AMP-dependent regulation of a high affinity serotonin transporter in the human placental choriocarcinoma cell line (JAR). J Biol Chem 266:15750–15757

    Google Scholar 

  22. Cooper DN, Krawczak M (1993) Human gene mutation. Bios Scientific, Oxford

    Google Scholar 

  23. Corey JL, Davidson N, Lester HA, Brecha N, Quick MW (1994) Protein kinase C modulates the activity of a cloned γ-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter. J Biol Chem 269:14759–14767

    CAS  PubMed  Google Scholar 

  24. Cortes R, Soriano E, Pazos A, Probst A, Palacios JM (1988) Autoradiography of antidepressant binding sites in the human brain: localization using [3H]imipramine and [3H]paroxetine. Neuroscience 27:473–496

    Google Scholar 

  25. Dave V, Kimelberg HK (1994) Na+-dependent, fluoxetine-sensitive serotonin uptake by astrocytes tissue-printed from rat cerebral cortex. J Neurosci 14:4972–4986

    Google Scholar 

  26. Di Bella D, Catalano M, Balling U, Smeraldi E, Lesch KP (1995) Systematic screening for mutations in the coding region of the 5-HTT gene using PCR and DGGE. Psychiatr Genet 5:S100

    Google Scholar 

  27. Donovan DM, Vandenbergh DJ, Perry MP, Bird GS, Ingersoll R, Nanthakumar E, Uhl GR (1995) Human and mouse dopamine transporter genes: conservation of 5′-flanking sequence elements and gene structures. Brain Res Mol Brain Res 30:327–335

    Google Scholar 

  28. Edwards RH (1992) Transport of neurotransmitters into synaptic vesicles. Curr Opin Neurobiol 2:586–594

    Google Scholar 

  29. Ellis PM, Salmond C (1994) Imipramine binding in depression: a meta-analysis. Biol Psychiatry 36:292–299

    Google Scholar 

  30. Erickson J, Eiden L, Hoffman B (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci USA 89:10993–10997

    Google Scholar 

  31. Erickson JD, Varoqui H, Schäfer MKH, Modi W, Diebler MF, Weihe E, Rand J, Eiden LE, Bonner TI, Usdin TB (1994) Functional identification of a vesicular acetylcholine transporter and its expression from a “cholinergic” gene locus. J Biol Chem 269:21929–21932

    CAS  PubMed  Google Scholar 

  32. Fairman WA, Vandenberg RJ, Arriza JL, Kavanaugh MP, Amara SG (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375:599–603

    Google Scholar 

  33. Figlewicz DP, Szot P, Israel PA, Payne CA, Dorsa DM (1993) Insulin reduces norepinephrine transporter mRNA in vivo in rat locus ceruleus. Brain Res 602:161–164

    Google Scholar 

  34. Gerlach M, Riederer P, Przuntek H, Youdim MBH (1991) MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease. Eur J Pharmacol Mol Pharmacol Sec 208:273–286

    Google Scholar 

  35. Giros B, Caron MG (1993) Molecular characterization of the dopamine Transporter. Trends Pharmacol Sci 14:43–49

    Google Scholar 

  36. Giros B, Wang YM, Suter S, McLeskey SB, Pifl C, Caron MG (1994) Delineation of discrete Domains for substrate, cocaine and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. J Biol Chem 269:15985–15988

    Google Scholar 

  37. Giros B, Jaber M, Jones S, Wightman R, Caron M (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612

    Article  CAS  PubMed  Google Scholar 

  38. Guastella J, Nelson N, Nelson H, Czyzyk L, Keynan S, Miedel MC, Davidson N, Lester H, Kanner BI (1990) Cloning and expression of a rat brain GABA transporter. Science 249:1303–1306

    Google Scholar 

  39. Guastella J, Brecha N, Weigmann C, Lester HA, Davidson N (1992) Cloning, expression, and localization of a rat brain high-affinity glycine transporter. Proc Natl Acad Sci USA 89:7189–7193

    Google Scholar 

  40. Haberland N, Hatey L (1987) Studies in postmortem dopamine uptake. II. Alterations of synaptosomal catecholamine uptake in postmortem brain regions in schizophrenia. J Neural Transm 68:303–313

    Google Scholar 

  41. Heils A, Teufel A, Petri S, Seemann M, Bengel D, Balling U, Riederer P, Lesch KP (1995) Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm 102:247–254

    Google Scholar 

  42. Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel B, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem (in press)

  43. Hensler JG, Ferry RC, Labow DM, Kovachich GB, Frazer A (1994) Quantitative autoradiography of the serotonin transporter to assess the distribution of serotonergic projections from the dorsal raphe nucleus. Synapse 17:1–15

    Google Scholar 

  44. Hoffman BJ, Mezey E, Brownstein M (1991) Cloning of a serotonin transporter affected by antidepressants. Science 254:579–580

    Google Scholar 

  45. Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abidargham A, Wallace E, Baldwin RM, Zeaponce Y, Zoghbi S, Wang S, Gao Y, Neumeyer JL, Charney DS, Hoffer PB, Marek KL (1993) Single-photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson's disease. Proc Natl Acad Sci USA 90:11965–11969

    Google Scholar 

  46. Jayanthi LD, Ramamoorthy S, Mahesh VB, Leibach FH, Ganapathy V (1994) Calmodulin-dependent regulation of the catalytic function of the human serotonin transporter in placental choriocarcinoma cells. J Biol Chem 269:14424–14429

    Google Scholar 

  47. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE (1993) Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 8:315–336

    Google Scholar 

  48. Kanai Y, Hediger MA (1993) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471

    Google Scholar 

  49. Kanai Y, Smith CP, Hediger MA (1993) A new family of neurotransmitter transporters: the high-affinity glutamate transporters. FASEB J 7:1450–1459

    Google Scholar 

  50. Kennedy GC, German MS, Rutter WJ (1995) The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription. Nature Genet 9:293–298

    Google Scholar 

  51. Kilbourn MR, Dasilva JN, Frey KA, Koeppe RA, Kuhl DE (1993) In vivo imaging of vesicular monoamine transporters in human brain using (C11) tetrabenazine and positron emission tomography. J Neurochem 60:2315–2318

    Google Scholar 

  52. Kitayama S, Shimada S, Xu H, Markham L, Donovan DM, Uhl GR (1992) Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine bindung. Proc Natl Acad Sci USA 89:7782–7785

    Google Scholar 

  53. Lehericy S, Brandel JP, Hirsch EC, Anglade P, Villares J, Scherman D, Duyckaerts C, Javoy-Agid F, Agid Y (1994) Monoamine vesicular uptake sites in patients with Parkinson's disease and Alzheimer's disease, as measured by tritiated dihydrotetrabenazine autoradiography. Brain Res 659:1–9

    Google Scholar 

  54. Leroux-Nicollet I, Costentin J (1994) Comparison of the subregional distributions of the monoamine vesicular transporter and dopamine uptake complex in the rat striatum and changes during aging. J Neural Transm 97:93–106

    Google Scholar 

  55. Lesch KP, Beckmann H (1993) Neurotransporter: neue Aspekte zum Wirkmechanismus psychotroper Substanzen. Nervenarzt 64:75–79

    Google Scholar 

  56. Lesch KP, Bengel D (1995) Neurotransmitter reuptake mechanisms: targets for drugs to study and treat psychiatric, neurological and neurodegenerative disorders. CNS Drugs 4:302–322

    Google Scholar 

  57. Lesch KP, Aulakh CS, Wolozin BL, Tolliver TJ, Hill JL, Murphy DL (1993) Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants. Mol Brain Res 17:31–35

    Google Scholar 

  58. Lesch KP, Gross J, Wolozin BL, Murphy DL, Riederer P (1993) Extensive sequence divergence between the human and rat brain vesicular monoamine transporter: possible evidence for species differences in the susceptibility to MPP+. J Neural Transm 93:75–82

    Google Scholar 

  59. Lesch KP, Wolozin BL, Murphy DL, Riederer P (1993) Primary structure of the human platelet serotonin (5-HT) uptake site: identity with the brain 5-HT transporter. J Neurochem 60:2319–2322

    Google Scholar 

  60. Lesch KP, Gross J, Riederer P, Murphy DL (1994) Direct sequencing of the reserpine-sensitive vesicular monoamine transporter in unipolar depression and bipolar disorder. Psychiatr Genet 4:153–160

    Google Scholar 

  61. Lesch KP, Franzek E, Gross J, Wolozin BL, Riederer P, Murphy DL (1995) Primary structure of the serotonin transporter in unipolar depression and bipolar disorder. Biol Psychiatry 37:215–223

    Google Scholar 

  62. Levi G, Raiteri M (1993) Carrier-mediated release of neurotransmitters. Trends Neurosci 16:415–419

    Google Scholar 

  63. Liu QR, Lopez-Corcuera B, Mandiyan S, Nelson H, Nelson N (1992) Molecular characterization of four pharmacologically distinct γ-aminobutyric acid transporters in mouse brain. J Biol Chem 268:2106–2112

    Google Scholar 

  64. Liu QR, Nelson H, Mandiyan S, Lopez-Corcuera B, Nelson N (1992) Cloning and expression of a glycine transporter from mouse brain. FEBS Lett 305:110–114

    Google Scholar 

  65. Liu Y, Peter D, Roghani A, Schuldiner S, Prive GG, Eisenberg D, Brecha N, Edwards RH (1992) A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70:539–551

    Article  CAS  PubMed  Google Scholar 

  66. Mager S, Min C, Henry DJ, Chavkin C, Hoffman BJ, Davidson N, Lester HA (1994) Conducting states of a mammalian serotonin transporter. Neuron 12:845–859

    Google Scholar 

  67. Mayser W, Betz H, Schloss P (1991) Isolation of cDNA encoding a novel member of the neurotransmitter transporter gene family. FEBS Lett 295:203–206

    Google Scholar 

  68. Mayser W, Schloss P, Betz H (1992) Primary structure and functional expression of a choline transporter expressed in the rat nervous system. FEB Lett 305:31–36

    Google Scholar 

  69. Meltzer H, Arora R, Baber R, Tricou B (1981) Serotonin uptake in blood platelets of psychiatric patients. Arch Gen Psychiatry 38:1322–1329

    Google Scholar 

  70. Meltzer H, Arora RC (1988) Genetic control of serotonin uptake in blood platelets: a twin study. Psychiatry Res 24:263–269

    Google Scholar 

  71. Miller KJ, Hoffman BJ (1994) Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP. J Biol Chem 269:27351–27356

    Google Scholar 

  72. Milner HE, Beliveau R, Jarvis SM (1994) The in situ size of the dopamine transporter is a tetramer as estimated by radiation inactivation. Biochim Biophys Acta 1190:185–187

    Google Scholar 

  73. Owen MJ, Nemeroff CB (1994) The role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 40:288–295

    CAS  PubMed  Google Scholar 

  74. Patel AP, Cerruti C, Vaughan RA, Kuhar MI (1995) Developmentally regulated glycosylation of dopamine transporter. Brain Res Dev Brain Res 83:53–58

    Google Scholar 

  75. Pearce RKB, Seeman P, Jellinger K, Tourtellotte W (1989) Dopamine uptake sites and dopamine receptors in Parkinson's disease and schizophrenia. Eur Neurol 30:9–14

    Google Scholar 

  76. Perry E, Marshall E, Blessed G, Tomlinson B, Perry R (1983) Decreased imipramine binding in the brains of patients with depressive illness. Br J Psychiatry 142:188–192

    Google Scholar 

  77. Peter D, Jimenez J, Liu YJ, Kim J, Edwards RH (1994) The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem 269:7231–7237

    Google Scholar 

  78. Pifl C, Drobny H, Reither H, Hornykiewicz O, Singer EA (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol 47:368–373

    Google Scholar 

  79. Pines G, Danbolt NC, Bjoras M, Zhang Y, Bendahan A, Eide L, Koepsell H, Storm-Mathisen J, Seeberg E, Kanner BI (1993) Cloning and expression of a rat brain l-glutamate transporter. Nature 360:464–466

    Google Scholar 

  80. Ramamoorthy S, Bauman A, Moore K, Han H, Yang-Feng T, Chang A, Ganapathy V, Blakely R (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 90:2542–2546

    CAS  PubMed  Google Scholar 

  81. Ramamoorthy S, Cool DR, Mahesh VB, Leibach FH, Melikian HE, Blakely RD, Ganapathy V (1993) Regulation of the human serotonin transporter: cholera toxin-induced stimulation of serotonin uptake in human placental choriocarcinoma cells is accompanied by increased serotonin transporter mRNA levels and serotonin transporter-specific ligand binding. J Biol Chem 268:21626–21631

    Google Scholar 

  82. Roghani A, Feldman J, Kohan SA, Shirzadi A, Gundersen CB, Brecha N, Edwards RH (1994) Molecular cloning of a putative vesicular transporter for acetylcholine. Proc Natl Acad Sci USA 91:10620–10624

    Google Scholar 

  83. Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral scerosis. New Engl J Med 326:1464–1468

    Google Scholar 

  84. Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713–725

    Google Scholar 

  85. Rudnick G, Steiner-Murdoch S, Fishkes H, Stern-Bach Y, Schuldiner S (1990) Energetics of reserpine binding and occlusion by the chromaffin granule biogenic amine transporter. Biochemistry 29:603–608

    Google Scholar 

  86. Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:78–84

    Google Scholar 

  87. Rudnick G, Wall SC (1993) Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters. Mol Pharmacol 43:271–276

    Google Scholar 

  88. Schloss P, Betz H (1995) Heterogeneity of antidepressant binding sites on the recombinant rat serotonin transporter SERT1. Biochemistry 34:12590–12595

    Google Scholar 

  89. Schuldiner S, Liu Y, Edwards RH (1993) Reserpine binding to a vesicular amine transporter expressed in chinese haster ovary fibroblasts. J Biol Chem 268:29–34

    Google Scholar 

  90. Schuldiner S, Steiner-Mordoch S, Yelin R, Wall SC, Rudnick G (1993) Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters. Mol Pharmacol 44:1227–1231

    Google Scholar 

  91. Scott HL, Tannenberg AE, Dodd PR (1995) Variant forms of neuronal glutamate transporter sites in Alzheimer's disease cerebral cortex. J Neurochem 64:2193–2202

    Google Scholar 

  92. Sen D, Gilbert W (1990) A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature 344:410–414

    Google Scholar 

  93. Simpson MDC, Slater P, Royston MC, Deakin JFW (1992) Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophrenia. Psychiatry Res 42:273–282

    Google Scholar 

  94. Smith KE, Borden LA, Hartig PR, Branchek T, Weinshank RL (1992) Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron 8:927–935

    Google Scholar 

  95. Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA (1994) Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: potential role in dicarboxylic aminoaciduria and neurodegnerative disorders. Genomics 20:335–336

    Google Scholar 

  96. Stahl S, Woo D, Mefford I, Berger P, Ciaranello R (1983) Hyperserotonemia and platelet serotonin uptake in schizophrenia and affective disorders. Am J Psychiatry 140:26–31

    Google Scholar 

  97. Stanley M, Virgilio J, Gershon S (1982) Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science 216:1337–1339

    Google Scholar 

  98. Storck T, Schulte S, Hofmann K, Stoffel W (1992) Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter in rat brain. Proc Natl Acad Sci USA 89:10955–10959

    Google Scholar 

  99. Tanner C, Langston J (1990) Do environmantal toxins cause Parkinson's disease? a critical review. Neurology 40:17–30

    Google Scholar 

  100. Tate CG, Blakely RD (1994) The effect of N-linked glycosylation on activity of the Na+- and Cl−-dependent serotonin transporter expressed using recombinant baculovirus in insect cells. J Biol Chem 269:26303–26310

    Google Scholar 

  101. Uhl GR, Johnson PS (1994) Neurotransmitter transporters: three important gene families for neuronal function. J Exp Biol 196:229–236

    Google Scholar 

  102. Usdin TB, Eiden LE, Bonner TI, Erickson JD (1995) Molecular biology of the vesicular ACh transporter. Trends Neurosci 18:218–224

    Google Scholar 

  103. Vingerhoets FJG, Snow BJ, Tetrud JW, Langston JW, Schulzer M, Calne DB (1994) Positron Emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions. Ann Neurol 36:765–770

    Google Scholar 

  104. Virmani MA, Conti R, Spadoni A, Rossi S, Arrigoni-Martelli E (1994) {spl-Carnitine uptake into primary rat cortical cultures: interaction with GABA}. Mol Brain Res 25:105–112

    Google Scholar 

  105. Wang JB, Moriwaki A, Uhl GR (1995) Dopamine transporter cysteine mutants: second extracellular loop cysteines are required for transporter expression. J Neurochem 64:1416–1419

    Google Scholar 

  106. Zanchin G, De-Boni A, Lauria G, Maggioni F, Rossi P, Villacara A (1995) Synaptosomal glutamate uptake in a model of experimental cerebral ischemia. Neurochem Res 20:195–199

    Google Scholar 

  107. Zottola RJ, Cloherty EK, Coderre PE, Hansen A, Hebert DN, Carruthers A (1995) Glucose transporter function is controlled by transporter oligomeric structure: single intramolecular disulfide promotes GLUT1 tetramerization. Biochemistry 34:9734–9747

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, D-97080, Würzburg, Germany

    K. P. Lesch, A. Heils & P. Riederer

Authors
  1. K. P. Lesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Heils
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Riederer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lesch, K.P., Heils, A. & Riederer, P. The role of neurotransporters in excitotoxicity, neuronal cell death, and other neurodegenerative processes. J Mol Med 74, 365–378 (1996). https://doi.org/10.1007/BF00210631

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00210631

Key words

Search

Navigation