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Therapeutic Potential of Nerve Growth Factors in Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is a neurodegenerative syndrome which primarily affects dopamine-producing neurons of the substantia nigra, resulting in poverty and slowness of movement, instability of gait and posture, and tremor at rest in individuals with the disease. While symptoms of the disease can be effectively managed for several years with available drugs, the syndrome is progressive and the efficacy of standard drugs wanes with time. One experimental approach to therapy is to use natural and synthetic molecules which promote survival and growth of dopaminergic neurons, so-called ‘neurotrophic factors’, to stabilise the diminishing population of dopaminergic neurons and stimulate compensation and growth in these cells. In this review, we examine the available evidence on 29 molecules with neurotrophic properties for dopaminergic neurons. The properties of these molecules provide ample reasons for optimism that a neurotrophic strategy can be developed that would provide a significant treatment option for patients with PD. While the search continues for even more specific, potent and long-lasting agents, the single greatest challenge is the development of techniques for targeted delivery of these molecules.

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References

  1. Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237: 1154–61

    PubMed  CAS  Google Scholar 

  2. Davies AM. The emerging generality of neurotrophic hypothesis. Trends Neurosci 1988; 11: 243–4

    PubMed  CAS  Google Scholar 

  3. Hefti F. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci 1986; 6: 2155–62

    PubMed  CAS  Google Scholar 

  4. Kromer LF. Nerve growth factor treatment after brain injury prevents neuronal death. Science 1987; 235: 214–6

    PubMed  CAS  Google Scholar 

  5. Williams LR, Varon S, Peterson GM, et al. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci USA 1986; 83: 9231–5

    PubMed  CAS  Google Scholar 

  6. Williams LR. Exogenous nerve growth factor stimulates choline acetyltransferase activity in aging Fischer 344 male rats. Neurobiol Aging 1991; 12: 39–46

    PubMed  CAS  Google Scholar 

  7. Lapchak PA. Therapeutic potential for nerve growth factor in Alzheimer’s disease: insights from pharmacological studies using lesioned cholinergic neurons. Rev Neurosci 1992; 3: 109–18

    PubMed  CAS  Google Scholar 

  8. Mufson EJ, Conner JM, Kordower JH. Nerve growth factor in Alzheimer’s disease: defective retrograde transport to nucleus basalis. Neuroreport 1995; 6: 1063–6

    PubMed  CAS  Google Scholar 

  9. Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966; 18: 925–64

    PubMed  CAS  Google Scholar 

  10. Yahr MD, Duvoisin RC, Schear MJ, et al. Treatment of parkinsonism with levodopa. Arch Neurol 1969; 21: 343–54

    PubMed  CAS  Google Scholar 

  11. Clough CG. Parkinson’s disease: management. Lancet 1991; 337: 1324–7

    PubMed  CAS  Google Scholar 

  12. Jonsson G, Sachs C. Effects of 6-hydroxydopamine on the uptake and storage of noradrenaline in sympathetic adrenergic neurons. Eur J Pharmacol 1970; 9: 141–55

    PubMed  CAS  Google Scholar 

  13. Marshall JF, Ungerstedt U. Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J Pharmacol 1977; 41: 361–7

    PubMed  CAS  Google Scholar 

  14. Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 1970; 24: 485–93

    PubMed  CAS  Google Scholar 

  15. Sauer H, Oertel WH. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 1994; 59: 401–15

    PubMed  CAS  Google Scholar 

  16. Dunnett SB, Whishaw IQ, Rogers DC, et al. Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions. Brain Res 1987; 415: 63–78

    PubMed  CAS  Google Scholar 

  17. Langston JW, Ballard P, Tetrud JW, et al. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979–80

    PubMed  CAS  Google Scholar 

  18. Heikkila RE, Hess A, Duvoisin RC. Dopaminergic neurotoxicity of l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine in mice. Science 1984; 224: 1451–3

    PubMed  CAS  Google Scholar 

  19. Hokfelt T, Ungerstedt U. Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurons: an electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro-striatal dopamine system. Brain Res 1973; 60: 269–97

    PubMed  CAS  Google Scholar 

  20. Hoffer BJ, Hoffman A, Bowenkamp K, et al. Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci Lett 1994; 182: 107–11

    PubMed  CAS  Google Scholar 

  21. Bowenkamp KE, Hoffman AF, Gerhardt GA, et al. Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons. J Comp Neurol 1995; 355: 479–89

    PubMed  CAS  Google Scholar 

  22. Lapchak PA, Miller PJ, Collins F, et al. Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: comparison of intraventricular and intranigral delivery. Neuroscience 1997; 78: 61–72

    PubMed  CAS  Google Scholar 

  23. Hagg T, Varon S. Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo. Proc Natl Acad Sci U S A 1993; 90: 6315–9

    PubMed  CAS  Google Scholar 

  24. Fallon J, Matthews RT, Hyman BT, et al. MPP+ produces progressive neuronal degeneration which is mediated by oxidative stress. Exp Neurol 1997; 144: 193–8

    PubMed  CAS  Google Scholar 

  25. Vingerhoets FJ, Snow BJ, Tetrud JW, et al. Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions. Ann Neurol 1994; 36: 765–70

    PubMed  CAS  Google Scholar 

  26. Pezzoli G, Zecchinelli A, Ricciardi S, et al. Intraventricular infusion of epidermal growth factor restores dopaminergic pathway in hemiparkinsonia rats. Mov Disord 1991; 6: 281–7

    PubMed  CAS  Google Scholar 

  27. Haug, H. Are neurons of the human cerebral cortex really lost during aging? A morphometric examination. In: Traber J, Gispen WH, editors. Senile dementia of the Alzheimer type. Berlin: Springer-Verlag, 1985: 150–63

    Google Scholar 

  28. Terry RD, DeTeresa R, Hansen LA. Neocortical cell counts in normal human adult aging. Ann Neurol 1987; 21: 530–9

    PubMed  CAS  Google Scholar 

  29. Engele J, Bohn MC. The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia [published erratum appears in J Neurosci 1992; 12 (3): 685]. J Neurosci 1991; 11: 3070–8

    PubMed  CAS  Google Scholar 

  30. Mena MA, Casarejos MJ, Gimenez-Gallego G, et al. Fibroblast growth factors: structure-activity on dopamine neurons in vitro. J Neurol Transm Park Dis Dement Sect 1995; 9: 1–14

    CAS  Google Scholar 

  31. Otto D, Unsicker K. FGF-2-mediated protection of cultured mesencephalic dopaminergic neurons against MPTP and MPP+: specificity and impact of culture conditions, non-dopaminergic neurons, and astroglial cells. J Neurosci Res 1993; 34: 382–93

    PubMed  CAS  Google Scholar 

  32. Ferrari G, Minozzi MC, Toffano G, et al. Basic fibroblast growth factor promotes the survival and development of mesencephalic neurons in culture. Dev Biol 1989; 133: 140–7

    PubMed  CAS  Google Scholar 

  33. Jones KR, Farinas I, Backus C, et al. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 1994; 76: 989–99

    PubMed  CAS  Google Scholar 

  34. Park TH, Mytilineou C. Protection from l-methyl-4-phenylpyridinium (MPP+) toxicity and stimulation of regrowth of MPP(+)-damaged dopaminergic fibers by treatment of mesencephalic cultures with EGF and basic FGF. Brain Res 1992; 599: 83–97

    PubMed  CAS  Google Scholar 

  35. Knusel B, Michel PP, Schwaber JS, et al. Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors. J Neurosci 1990; 10: 558–70

    PubMed  CAS  Google Scholar 

  36. Mayer E, Dunnett SB, Pellitteri R, et al. Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons: I. effects in vitro. Neuroscience 1993; 56: 379–88

    PubMed  CAS  Google Scholar 

  37. Otto D, Unsicker K. Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 1990; 10: 1912–21

    PubMed  CAS  Google Scholar 

  38. Chadi G, Moller A, Rosen L, et al. Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion. Exp Brain Res 1993; 97: 145–58

    PubMed  CAS  Google Scholar 

  39. Date I, Notter MF, Feiten SY, et al. MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). Brain Res 1990; 526: 156–60

    PubMed  CAS  Google Scholar 

  40. Alexi T, Hefti F. Neurotrophin-4/5 selectively protects nigral calbindin-containing neurons in rats with medial forebrain transections. Neuroscience 1996; 72: 911–21

    PubMed  CAS  Google Scholar 

  41. Otto D, Unsicker K. FGF-2 in the MPTP model of Parkinson’s disease: effects on astroglial cells. Glia 1994; 11: 47–56

    PubMed  CAS  Google Scholar 

  42. Casper D, Mytilineou C, Blum, M. EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture. J Neurosci Res 1991; 30: 372–81

    PubMed  CAS  Google Scholar 

  43. Hadjiconstantinou M, Fitkin JG, Dalia A, et al. Epidermal growth factor enhances striatal dopaminergic parameters in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse. J Neurochem 1991; 57: 479–82

    PubMed  CAS  Google Scholar 

  44. Casper D, Roboz GJ, Blum M. Epidermal growth factor and basic fibroblast growth factor have independent actions on mesencephalic dopamine neurons in culture. J Neurochem 1994; 62: 2166–75

    PubMed  CAS  Google Scholar 

  45. Alexi T, Hefti F. Trophic actions of transforming growth factor alpha on mesencephalic dopaminergic neurons developing in culture. Neuroscience 1993; 55: 903–18

    PubMed  CAS  Google Scholar 

  46. Widmer HR, Alexi T, Valverde J, et al. TGF alpha Stimulation of phosphatidylinositol hydrolysis in mesencephalic cultures requires neuron-glia interactions. Neuroreport 1993; 4: 407–10

    PubMed  CAS  Google Scholar 

  47. Nikkhah G, Odin P, Smits A, et al. Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture. Exp Brain Res 1993; 92: 516–23

    PubMed  CAS  Google Scholar 

  48. Poulsen KT, Annanini MP, Klein RD, et al. TGF beta 2 and TGF beta 3 are potent survival factors for midbrain dopaminergic neurons. Neuron 1994; 13: 1245–52

    PubMed  CAS  Google Scholar 

  49. Krieglstein K, Unsicker K. Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. Neuroscience 1994; 63: 1189–96

    PubMed  CAS  Google Scholar 

  50. Krieglstein K, Suter-Crazzolara C, Fischer WH, et al. TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. EMBO J 1995; 14: 736–42

    PubMed  CAS  Google Scholar 

  51. Krieglstein K, Suter-Crazzolara C, Hotten G, et al. Trophic and protective effects of growth/differentiation factor 5, a member of the transforming growth factor-beta superfamily, on midbrain dopaminergic neurons. J Neurosci Res 1995; 42: 724–32

    PubMed  CAS  Google Scholar 

  52. Jordan J, Bottner M, Schluesener HJ, et al. Bone morphogenetic proteins: neurotrophic roles for midbrain dopaminergic neurons and implications of astroglial cells. Eur J Neurosci 1997; 9: 1699–709

    PubMed  CAS  Google Scholar 

  53. Milbrandt J, de Sauvage FJ, Fahrner TJ, et al. Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 1998; 20: 245–53

    PubMed  CAS  Google Scholar 

  54. Tseng JL, Bruhn SL, Zurn AD, et al. Neurturin protects dopaminergic neurons following medial forebrain bundle axotomy. Neuroreport 1998; 9: 1817–22

    PubMed  CAS  Google Scholar 

  55. Lin L-F H, Doherty DH, Lile JD, et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993; 260: 1130–2

    PubMed  CAS  Google Scholar 

  56. Clarkson ED, Zawada WM, Freed CR. GDNF reduces apoptosis in dopaminergic neurons in vitro. Neuroreport 1995; 7: 145–9

    PubMed  CAS  Google Scholar 

  57. Hou J-G G, Lin L-FH, Mytilineou C. Glial cell line-derived neurotrophic factor exerts neurotrophic effects on dopaminergic neurons in vitro and promotes their survival and re-growth after damage by 1-methyl-4-phenylpyridinium. J Neurochem 1996; 66: 74–82

    PubMed  CAS  Google Scholar 

  58. Hudson J, Granholm AC, Gerhardt GA, et al. Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo. Brain Res Bull 1995; 36: 425–32

    PubMed  CAS  Google Scholar 

  59. Shults CW, Kimber T, Martin D. Intrastriatal injection of GDNF attenuates the effects of 6-hydroxydopamine. Neuroreport 1996; 7: 627–31

    PubMed  CAS  Google Scholar 

  60. Martin D, Miller G, Cullen T, et al. Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and behavior in rats. Eur J Pharmacol 1996; 317: 247–56

    PubMed  CAS  Google Scholar 

  61. Hebert MA, Van Horne CG, Hoffer BJ, et al. Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis. J Pharmacol Exp Ther 1996; 279: 1181–90

    PubMed  CAS  Google Scholar 

  62. Gash DM, Zhang Z, Cass WA, et al. Morphological and functional effects of intranigrally administered GDNF in normal rhesus monkeys. J Comp Neurol 1995; 363: 345–58

    PubMed  CAS  Google Scholar 

  63. Beck KD, Irwin I, Valverde J, et al. GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis. Neuron 1996; 16: 665–73

    PubMed  CAS  Google Scholar 

  64. Lapchak PA, Miller PJ, Jiao S. Glial cell line-derived neurotrophic factor induces the dopaminergic and cholinergic phenotype and increases locomotor activity in aged Fischer 344 rats. Neuroscience 1997; 77: 745–52

    PubMed  CAS  Google Scholar 

  65. Bowenkamp KE, Lapchak PA, Hoffer BJ, et al. Glial cell line-derived neurotrophic factor reverses motor impairment in 16–17 month old rats. Neurosci Lett 1996; 211: 81–4

    PubMed  CAS  Google Scholar 

  66. Cass WA. GDNF selectively protects dopamine neurons over serotonin neurons against the neurotoxic effects of methamphetamine. J Neurosci 1996; 16: 8132–9

    PubMed  CAS  Google Scholar 

  67. Beck KD, Valverde J, Alexi T, et al. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 1995; 373: 339–41

    PubMed  CAS  Google Scholar 

  68. Lu X, Hagg T. Glial cell line-derived neurotrophic factor prevents death, but not reductions in tyrosine hydroxylase, of injured nigrostriatal neurons in adult rats. J Comp Neurol 1997; 388: 484–94

    PubMed  CAS  Google Scholar 

  69. Tseng JL, Baetge EE, Zurn AD, et al. GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J. Neurosci 1997; 17: 325–33

    PubMed  CAS  Google Scholar 

  70. Kearns CM, Gash DM. GDNF protects nigral DA neurons against 6-hydroxydopamine in vivo. Brain Res 1995; 672: 104–11

    PubMed  CAS  Google Scholar 

  71. Kearns CM, Cass WA, Smoot K, et al. GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. J Neurosci 1997; 17: 7111–8

    PubMed  CAS  Google Scholar 

  72. Opacka-Juffry J, Ashworth S, Hume SP, et al. GDNF protects against 6-OHDA nigrostriatal lesion: in vivo study with microdialysis and PET. Neuroreport 1995; 7: 348–52

    PubMed  CAS  Google Scholar 

  73. Sauer I, Rosenblad C, Bjorklund A. Glial cell-line derived neurotrophic factor but not transforming growth factor Beta3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesions. Proc Natl Acad Sci U S A 1995; 92: 8935–9

    PubMed  CAS  Google Scholar 

  74. Tomac A, Lindqvist E, Lin L-FH, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 1995; 373: 335–9

    PubMed  CAS  Google Scholar 

  75. Winkler C, Sauer H, Lee CS, et al. Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 1996; 16: 7206–15

    PubMed  CAS  Google Scholar 

  76. Bowenkamp KE, Lapchak PA, Hoffer BJ, et al. Intracerebral glial cell line-derived neurotrophic factor improves motor function and supports nigrostriatal dopamine neurons in bilaterally 6-hydroxydopamine lesioned rats. Exp Neurol 1997; 145: 104–7

    PubMed  CAS  Google Scholar 

  77. Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380: 252–5

    PubMed  CAS  Google Scholar 

  78. Lin L-F H. Glial cell line-derived neurotrophic factor (GDNF): a comprehensive review. Neurol Notes 1996; 11: 3–7

    Google Scholar 

  79. Yurek DM. Intranigral transplants of fetal ventral mesencephalic tissue attenuate D1-agonist-induced rotational behavior. Exp Neurol 1997; 143: 1–9

    PubMed  CAS  Google Scholar 

  80. Spina M, Squinto SP, Miller J, et al. Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpydridinium ion toxicity: involvement of the glutathione system. J Neurochem 1992; 59: 99–105

    PubMed  CAS  Google Scholar 

  81. Knusel B, Winslow JW, Rosenthal A, et al. Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci U S A 1991; 88: 961–5

    PubMed  CAS  Google Scholar 

  82. Studer L, Spenger C, Seller RW, et al. Comparison of the effects of the neurotrophins on the morphological structure of dopaminergic neurons in cultures of rat substantia nigra. Eur J Neurosci 1995; 7: 223–33

    PubMed  CAS  Google Scholar 

  83. Hyman C, Hofer M, Barde Y-A, et al. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 1991; 350: 230–2

    PubMed  CAS  Google Scholar 

  84. Beck KD. Functions of brain-derived neurotrophic factor, insulin-like growth factor-1 and basic fibroblast growth factor in the development and maintenance of dopaminergic neurons. Prog Neurobiol 1994; 44: 497–516

    PubMed  CAS  Google Scholar 

  85. Hyman C, Juhasz M, Jackson C, et al. Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT -4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci 1994; 14: 335–47

    PubMed  CAS  Google Scholar 

  86. Zhou J, Bradford HF, Stern GM. The response of human and rat fetal ventral mesencephalon in culture to the brain-derived neurotrophic factor treatment. Brain Res 1994; 656: 147–56

    PubMed  CAS  Google Scholar 

  87. Blochl A, Sirrenberg C. Neurotrophins stimulate the release of dopamine from rat mesencephalic neurons via Trk and p75 lntr receptors. J Biol Chem 1996; 271: 21100–7

    PubMed  CAS  Google Scholar 

  88. Skaper SD, Negro A, Facci L, et al. Brain-derived neurotrophic factor selectively rescues mesencepahalic dopaminergic neurons from 2,4,5-trihydroxyphenylalanine-induced injury. J Neurosci Res 1993; 34: 478–87

    PubMed  CAS  Google Scholar 

  89. Altar CA, Boylan CB, Jackson C, et al. Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo. Proc Natl Acad Sci USA 1992; 89: 11347–51

    PubMed  CAS  Google Scholar 

  90. Altar CA, Boylan CB, Fritsche M, et al. The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic systems during behaviorally effective infusions to the substantia nigra. Exp Neurol 1994; 130: 31–40

    PubMed  CAS  Google Scholar 

  91. Martin-Iverson MT, Todd KG, Altar CA. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine. J Neurosci 1994; 14: 1262–70

    PubMed  CAS  Google Scholar 

  92. Shen R-Y, Altar CA, Chiodo LA. Brain-derived neurotrophic factor increased the electrical activity of pars compacta dopamine neurons in vivo. Proc Natl Acad Sci USA 1994; 91: 8920–4

    PubMed  CAS  Google Scholar 

  93. Altar CA, Boylan CB, Fritsche MF, et al. Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions. J Neurochem 1993; 63: 1021–32

    Google Scholar 

  94. Knusel B, Beck KD, Winslow JW, et al. Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci 1992; 12: 4391–402

    PubMed  CAS  Google Scholar 

  95. Hagg T. Neurotrophins prevent death and differentially affect tyrosine hydroxylase of adult rat nigrostriatal neurons in vivo. Exp Neurol 1998; 149: 183–92

    PubMed  CAS  Google Scholar 

  96. Chao MV, Hempstead BL. p75 and Trk: a two-receptor system. Trends Neurosci 1995; 18: 321–6

    PubMed  CAS  Google Scholar 

  97. Spenger C, Hyman C, Studer L, et al. Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal ventral mesencephalon. Exp Neurol 1995; 133: 50–63

    PubMed  CAS  Google Scholar 

  98. Nakao N, Brundin P, Funa K, et al. Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro. Dev Brain Res 1995; 90: 92–101

    CAS  Google Scholar 

  99. Zhou J, Bradford HF, Stern GM. The stimulatory effects of brain-derived neurotrophic factor on dopaminergic pheno-type expression of embryonic rat cortical neurons in vitro. Dev Brain Res 1994; 81: 318–24

    CAS  Google Scholar 

  100. von Coelln R, Unsicker K, Krieglstein K. Screening of interleukins for survival-promoting effects on cultured mesencephalic dopaminergic neurons from embryonic rat brain. Brain Res Dev Brain Res 1995; 89: 150–4

    Google Scholar 

  101. Akaneya Y, Takahashi M, Hatanaka H. Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Exp Neurol 1995; 136: 44–52

    PubMed  CAS  Google Scholar 

  102. Wang J, Bankiewicz KS, Plunkett RJ, et al. Intrastriatal implantation of interleukin-1. Reduction of parkinsonism in rats by enhancing neuronal sprouting from residual dopaminergic neurons in the ventral tegmental area of the midbrain. J Neurosurg 1994; 80: 484–90

    PubMed  CAS  Google Scholar 

  103. Magal E, Burnham P, Varon S, et al. Convergent regulation by ciliary neurotrophic factor and dopamine of tyrosine hydroxylase expression in cultures of rat substantia nigra. Neuroscience 1993; 52: 867–81

    PubMed  CAS  Google Scholar 

  104. Ostergaard K, Jones SA, Hyman C, et al. Effects of donor age and brain-derived neurotrophic factor on the survival of dopaminergic neurons and axonal growth in postnatal rat nigrostriatal cocultures. Exp Neurol 1996; 142: 340–50

    PubMed  CAS  Google Scholar 

  105. Ledeen RW. Biology of gangliosides: neurotogenic and neuronotrophic properties. J Neurosci Res 1984; 12: 147–59

    PubMed  CAS  Google Scholar 

  106. Leon A, Dal Toso R, Presti D, et al. Development and survival of neurons in dissociated fetal mesencephalic serum-free cell cultures: II. modulatory effects of gangliosides. J Neurosci 1988; 8: 746–53

    PubMed  CAS  Google Scholar 

  107. Dalia A, Neff NH, Hadjiconstantinou, M. GM1 ganglioside improves dopaminergic markers of rat mesencephalic cultures treated with MPP+. J Neurosci 1993; 13: 3104–11

    PubMed  CAS  Google Scholar 

  108. Hadjiconstantinou M, Rossetti ZL, Paxton RC, et al. Administration of GM1 ganglioside restores the dopamine content in striatum after chronic treatment with MPTP. Neuropharmacology 1986; 25: 1075–7

    PubMed  CAS  Google Scholar 

  109. Hadjiconstantinou M, Neff NH. Treatment with GMIa ganglioside restores striatal dopamine in the l-methyl-4-phenyl-1,2,3,6-tetrahlydropyridine-treated mouse. J Neurochem 1988; 51: 1190–5

    PubMed  CAS  Google Scholar 

  110. Hadjiconstantinou M, Neff NH. Differential recovery of dopamine synthetic enzymes following MPTP and the consequences of GM1 ganglioside treatment. Eur J Pharmacol 1990; 181: 137–9

    PubMed  CAS  Google Scholar 

  111. Hadjiconstantinou M, Weihmuller F, Neff NH. Treatment with GM1 ganglioside reverses dopamine D-2 receptor supersensitivity induced by the neurotoxin MPTP. Eur J Pharmacol 1989; 168: 261–4

    PubMed  CAS  Google Scholar 

  112. Hadjiconstantinou M, Mariani AP, Neff NH. GM1 ganglioside-induced recovery of nigrostriatal dopaminergic neurons after MPTP: an immunohistochemical study. Brain Res 1989; 484: 297–303

    PubMed  CAS  Google Scholar 

  113. Gupta M, Schwarz J, Chen XL, et al. Gangliosides prevent MPTP toxicity in mice-an immunocytochemical study. Brain Res 1990; 527: 330–4

    PubMed  CAS  Google Scholar 

  114. Weihmuller FB, Hadjiconstantinou M, Bruno JP, et al. Administration of GM1 ganglioside eliminates neuroleptic-induced sensorimotor deficits in MPTP-treated mice. Neurosci Lett 1988; 92: 207–12

    PubMed  CAS  Google Scholar 

  115. Weihmuller FB, Hadjiconstantinou M, Bruno JP, et al. Continued administration of GM1 ganglioside is required to maintain recovery from neuroleptic-induced sensorimotor deficits in MPTP-treated mice. Life Sci 1989; 45: 2495–502

    PubMed  CAS  Google Scholar 

  116. Janson AM, Agnati LF, Fuxe K, et al. GM1 ganglioside protects against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of nigrostriatal dopamine neurons in the black mouse. Acta Physiol Scand 1988; 132: 587–8

    PubMed  CAS  Google Scholar 

  117. Schneider JS, Pope A, Simpson K, et al. Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment. Science 1992; 256: 843–6

    PubMed  CAS  Google Scholar 

  118. Herrero MT, Perez-Otano I, Oset C, et al. GM-1 ganglioside promotes the recovery of surviving midbrain dopaminergic neurons in MPTP-treated monkeys. Neuroscience 1993; 56: 965–72

    PubMed  CAS  Google Scholar 

  119. Fadda E, Negro A, Facci L, et al. Ganglioside GM1 cooperates with brain-derived neurotrophic factor to protect dopaminergic neurons from 6-hydroxydopamine-induced degeneration. Neurosci Lett 1993; 159: 147–50

    PubMed  CAS  Google Scholar 

  120. Schneider JS, DiStefano L. Enhanced restoration of striatal dopamine concentrations by combined GM1 ganglioside and neurotrophic factor treatments. Brain Res 1995; 674: 260–4

    PubMed  CAS  Google Scholar 

  121. Hynes M, Porter JA, Chiang C, et al. Induction of midbrain dopaminergic neurons by sonic hedgehog. Neuron 1995; 15: 35–44

    PubMed  CAS  Google Scholar 

  122. Wang MZ, Jin P, Bumcrot DA, et al. Induction of dopaminergic neuron phenotype in the midbrain by sonic hedgehog protein. Nat Med 1995; 1: 1184–8

    PubMed  CAS  Google Scholar 

  123. Steiner JP, Dawson TM, Fotuhi M, et al. High brain densities of the immunophilin FKBP colocalized with calcineurin. Nature 1992; 358: 584–7

    PubMed  CAS  Google Scholar 

  124. Lyons WE, Steiner JP, Snyder SH, et al. Neuronal regeneration enhances the expression of the immunophilin FKBP-12. J Neurosci 1995; 15: 2985–94

    PubMed  CAS  Google Scholar 

  125. Costantini LC, Chaturvedi P, Armistead DM, et al. A novel immunophilin ligand: distinct branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of Parkinson’s disease. Neurobiol Dis 1998; 5: 97–106

    PubMed  CAS  Google Scholar 

  126. Steiner JP, Hamilton GS, Ross DT, et al. Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. Proc Natl Acad Sci USA 1997; 94: 2019–24

    PubMed  CAS  Google Scholar 

  127. Merlio J-P, Ernfors P, Jaber M, et al. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system. Neurosci 1992; 51: 513–32

    CAS  Google Scholar 

  128. Yan Q, Radeke MJ, Matheson CR, et al. Immunocytochemical localization of trkB in the central nervous system of the adult rat. J Comp Neurol 1997; 378: 135–57

    PubMed  CAS  Google Scholar 

  129. Altar CA, Criden MR, Lindsay RM, et al. Characterization and topography of high affinity [125I] neurotrophin-3 binding to mammalian brain. J Neurosci 1993; 13: 733–43

    PubMed  CAS  Google Scholar 

  130. Lindsay RM, Altar CA, Cedarbaum JM, et al. The therapeutic potential of neurotrophic factors in the treatment of Parkinson’s disease. Exp Neurol 1993; 124: 103–18

    PubMed  CAS  Google Scholar 

  131. Farrar WL, Kilian PL, Ruff MR, et al. Visualization and characterization of interleukin 1 receptors in brain. J Immunol 1987; 139: 459–63

    PubMed  CAS  Google Scholar 

  132. Smits A, Kato M, Westermark B, et al. Neurotrophic activity of platelet derived growth factor (PDGF): rat neuronal cells possess functional PDGF Beta-type receptors and respond to PDGF. Proc Natl Acad Sci U S A 1991; 88: 8159–63

    PubMed  CAS  Google Scholar 

  133. Adem A, Jossan SS, d’Argy R, et al. Insulin-like growth factor 1 (IGF-1) receptors in the human brain: quantitative autoradiographic localization. Brain Res 1989; 503: 299–303

    PubMed  CAS  Google Scholar 

  134. Kornblum HI, Hussain RJ, Bronstein JM, et al. Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain. J Comp Neurol 1997; 380: 243–61

    PubMed  CAS  Google Scholar 

  135. Trupp M, Belluardo N, Funakoshi H, et al. Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. J Neurosci 1997; 17: 3554–67

    PubMed  CAS  Google Scholar 

  136. Aroujo DM, Hilt DC, Miller PJ, et al. Ret receptor tyrosine kinase immunoreactivity is altered in glial cell line-derived neurotrophic factor responsive neurons following lesions of the nigrostriatal and septohippocampal pathways. Neurosci 1997; 80: 9–16

    Google Scholar 

  137. Trupp M, Arenas E, Fainzilber M, et al. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 1996; 381:785–9

    PubMed  CAS  Google Scholar 

  138. Treanor JJS, Goodman L, de Sauvage F, et al. Characterization of a multicomponent GDNF receptor. Nature 1996; 382: 80–3

    PubMed  CAS  Google Scholar 

  139. Hofer M, Pagliusi SR, Hohn A, et al. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 1990; 9: 2459–64

    PubMed  CAS  Google Scholar 

  140. Seroogy KB, Gall CM. Expression of neurotrophins by midbrain dopaminergic neurons. Exp Neurol 1993; 124: 119–28

    PubMed  CAS  Google Scholar 

  141. Gall CM, Gold SJ, Isackson PJ, et al. Brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in ventral midbrain regions containing dopaminergic neurons. Mol Cell Neurosci 1992; 2: 56–60

    Google Scholar 

  142. Seroogy KB, Lundgren KH, Tran TMD, et al. Dopaminergic neurons in rat ventral midbrain express brain derived neurotrophic factor and neurotrophin-3 mRNA’s. J Comp Neurol 1994; 342: 321–34

    PubMed  CAS  Google Scholar 

  143. Friedman WJ, Olson L, Persson, H. Cells that express brain-derived neurotrophic factor mRNA in the developing postnatal rat brain. Eur J Neurosci 1991; 3: 688–97

    PubMed  Google Scholar 

  144. Bean AJ, Elde R, Cao Y, et al. Expression of acidic and basic fibroblast growth factors in the sunstantia nigra of the rat, monkey, and human. Proc Natl Acad Sci U S A 1991; 88: 10237–41

    PubMed  CAS  Google Scholar 

  145. Chadi G, Cao Y, Pettersson RF, et al. Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Neurosci 1994; 61: 891–910

    CAS  Google Scholar 

  146. Tooyama I, Walker D, Yamada T, et al. High molecular weight basic fibroblast growth factor-like protein is localized to a subpopulation of mesencephalic dopaminergic neurons in the rat brain. Brain Res 1992; 593: 274–80

    PubMed  CAS  Google Scholar 

  147. Sasahara M, Fries JWU, Raines W, et al. PDGF B-Chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell 1991; 64: 217–27

    PubMed  CAS  Google Scholar 

  148. Seroogy KB, Han VKM, Lee DC. Regional expression of transforming growth factor-alpha mRNA in the rat central nervous system. Neurosci Lett 1991; 125: 241–5

    PubMed  CAS  Google Scholar 

  149. Schaar DG, Sieber B-A, Dreyfus CF, et al. Regional and cell-specific expression of GDNF in rat brain. Exp Neurol 1993; 124: 368–71

    PubMed  CAS  Google Scholar 

  150. Choi-Lundberg DL, Bohn MC. Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat. Dev Brain Res 1995; 85: 80–8

    CAS  Google Scholar 

  151. Springer JE, Mu X, Bergmann LW, et al. Expression of GDNF mRNA in rat and human nervous tissue. Exp Neurol 1994; 127: 167–70

    PubMed  CAS  Google Scholar 

  152. Blum M, Weickert CS. GDNF mRNA expression in normal postnatal development, aging and in weaver mutant mice. Neurobiol Aging 1995; 16: 925–9

    PubMed  CAS  Google Scholar 

  153. Yeh H-J, Ruit KG, Wang Y-X, et al. PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. Cell 1991; 64: 209–16

    PubMed  CAS  Google Scholar 

  154. Lazar LM, Blum M. Regional distribution and developmental expression of epidermal growth factor and transforming growth factor-alpha mRNA in mouse brain by a quantitative nuclease protection assay. J Neurosci 1992; 12: 1688–97

    PubMed  CAS  Google Scholar 

  155. Unsicker K, Flanders KC, Cissel DS, et al. Transforming growth factor beta isoforms in the adult rat central and periph eral nervous system. Neuroscience 1991; 44: 613–25

    PubMed  CAS  Google Scholar 

  156. Kawamoto Y, Nakamura S, Nakano S, et al. Immunohistochemical localization of brain-derived neurotrophic factor in adult rat brain. Neuroscience 1996; 74: 1209–26

    PubMed  CAS  Google Scholar 

  157. Conner JM, Lauterborn JC, Yan Q, et al. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal trans port. J Neurosci 1997; 17: 2295–313

    PubMed  CAS  Google Scholar 

  158. Maisonpierre PC, Belluscio L, Friedman B, et al. NT-3, BDNF, NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 1990; 5: 501–9

    PubMed  CAS  Google Scholar 

  159. Stromberg I, Bjorklund L, Johansson M, et al. Glial cell line-derived neurotrophic factor is expressed in the developing but not adult striatum and stimulates developing dopamine neurons in vivo. Exp Neurol 1993; 124: 401–12

    PubMed  CAS  Google Scholar 

  160. Nosrat CA, Tomac A, Lindqvist E, et al. Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous system. Cell Tissue Res 1996; 286: 191–207

    PubMed  CAS  Google Scholar 

  161. Wilcox JN, Derynck R. Localization of cells synthesizing transforming growth factor-alpha mRNA in the mouse brain. J Neurosci 1988; 8: 1901–4

    PubMed  CAS  Google Scholar 

  162. Fryer RH, Kaplan DR, Feinstein SC, et al. Developmental and mature expression of full-length and truncated Trk-B receptors in the rat forebrain. J Comp Neurol 1996; 374: 21–40

    PubMed  CAS  Google Scholar 

  163. Lamballe F, Smeyne RJ, Barbacid M. Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J Neurosci 1994; 14: 14–28

    PubMed  CAS  Google Scholar 

  164. Funa K, Yamada N, Brodin G, et al. Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain. Neuroscience 1996; 74(3): 825–33

    PubMed  CAS  Google Scholar 

  165. Schmidt-Kastner R, Wetmore C, Olson L. Comparative study of brain-derived neurotrophic factor messenger RNA and protein at the cellular level suggests multiple roles in hippocampus, striatum and cortex. Neuroscience 1996; 74: 161–83

    PubMed  CAS  Google Scholar 

  166. Okazawa H, Murata M, Watanabe M, et al. Dopaminergic stimulation up-regulates the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum. FEBS Lett 1992; 313: 138–42

    PubMed  CAS  Google Scholar 

  167. Schmidt-Kastner R, Tomac A, Hoffer B, et al. Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status. Mol Brain Res 1994; 26: 325–30

    PubMed  CAS  Google Scholar 

  168. Carrey PM, Ptak LR, Nath ST, et al. Striatal extracts from patients with Parkinson’s disease promote dopamine neuron growth in mesencephalic cultures. Exp Neurol 1993; 120: 149–52

    Google Scholar 

  169. Liu X, Ernfors P, Wu H, et al. Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 1995; 375: 238–41

    PubMed  CAS  Google Scholar 

  170. Moore MW, Klein RD, Farinas I, et al. Renal and neuronal abnormalities in mice lacking GDNF. Nature 1996; 382: 76–9

    PubMed  CAS  Google Scholar 

  171. Sanchez MP, Silos-Santiago I, Frisen J, et al. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996; 382: 70–3

    PubMed  CAS  Google Scholar 

  172. Granholm ACE, Srivastava N, Mott JL, et al. Morphological alterations in the peripheral and central nervous systems of mice lacking glial cell line-derived neurotrophic factor (GDNF): immunohistochemical studies. J Neurosci 1997; 17: 1168–78

    PubMed  CAS  Google Scholar 

  173. Zetterstrom RH, Solomin L, Jansson L, et al. Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997; 276: 248–50

    PubMed  CAS  Google Scholar 

  174. Xiao Q, Castillo SO, Nikodem VM. Distribution of messenger RNA’s for the orphan nuclear receptors Nurr1 and Nur77 (NGF1-B) in adult rat brain using in situ hybridization. Neuroscience 1996; 75: 221–30

    PubMed  CAS  Google Scholar 

  175. Zetterstrom RH, Williams R, Perlmann T, et al. Cellular expression of the immediate early transcription factors Nurrl and NGF1-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system. Brain Res 1996; 41: 111–20

    CAS  Google Scholar 

  176. Blum M. A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra. Nature Neurosci 1998; 1: 374–7

    PubMed  CAS  Google Scholar 

  177. Tooyama I, Kawamata T, Walker D, et al. Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson’s disease. Neurology 1993; 43: 372–6

    PubMed  CAS  Google Scholar 

  178. Fearnley J, Lees A. Pathology of Parkinson’s disease. In: Calne DB, editor. Neurodegenerative diseases. Philadelphia: WB. Saunders, 1994: 545–54

    Google Scholar 

  179. Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 1991; 114: 2283–301

    PubMed  Google Scholar 

  180. Szabo J. Organisation of the ascending striatal afferents in monkeys. J Comp Neurol 1980; 189: 307–21

    PubMed  CAS  Google Scholar 

  181. Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease: pathophysiologic and clinical implications. N Engl J Med 1988; 318: 876–80

    PubMed  CAS  Google Scholar 

  182. Tompkins MM, Basgall EJ, Zamrini E, et al. Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantial nigral neurons. Am J Pathol 1997; 150: 119–31

    PubMed  CAS  Google Scholar 

  183. Raff MC, Barres BA, Burne JF, et al. Programmed cell death and the control of cell survival: lessons from the nervous system. Science 1993; 262: 695–700

    PubMed  CAS  Google Scholar 

  184. Deckwerth TL, Johnson EM Jr. Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor. J Cell Biol 1993; 123: 1207–22

    PubMed  CAS  Google Scholar 

  185. Kastner A, Hirsch EC, Agid Y, et al. Tyrosine hydroxylase protein and messenger RNA in the dopaminergic nigral neurons of patients with Parkinson’s disease. Brain Res 1993; 606: 341–5

    PubMed  CAS  Google Scholar 

  186. Anderson KD, Alderson RF, Altar CA, et al. Differential distribution of exogenous BDNF, NGF, and NT-3 in the brain corresponds to the relative abundance and distribution of high-affinity and low-affinity neurotrophin receptors. J Comp Neurol 1995; 357: 296–317

    PubMed  CAS  Google Scholar 

  187. Yan Q, Matheson C, Sun J, et al. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression. Exp Neurol 1994; 127: 23–36

    PubMed  CAS  Google Scholar 

  188. Mufson EJ, Kroin JS, Liu Y-T, et al. Intrastriatal and intraventricular infusion of brain derived neurotrophic factor in the cynomologous monkey: distribution, retrograde transport and co-localization with substantia nigra dopamine-containing neurons. Neuroscience 1996; 71: 179–91

    PubMed  CAS  Google Scholar 

  189. Mufson EJ, Kroin JS, Sobreviela T, et al. Intrastriatal infusions of brain-derived neurotrophic factor: retrograde transport and colocalization with dopamine containing substantia nigra neurons in rat [published erratum appears in Exp Neurol 1994 Dec; 130 (2): 414] Exp Neurol 1994; 129: 15–26

    PubMed  CAS  Google Scholar 

  190. Lapchak PA, Jiao SS, Collins F, et al. Glial cell line-derived neurotrophic factor: distribution and pharmacology in the rat following a bolus intraventricular injection. Brain Res 1997; 747: 92–102

    PubMed  CAS  Google Scholar 

  191. Friden PM, Walus LR, Watson P, et al. Blood-brain barrier pen etration and in vivo activity of an NGF conjugate. Science 1993; 259: 373–7

    PubMed  CAS  Google Scholar 

  192. Kordower JH, Mufson EJ, Granholm AC, et al. Delivery of trophic factors to the primate brain. Exp Neurol 1993; 124: 21–30

    PubMed  CAS  Google Scholar 

  193. Kordower JH, Charles V, Bayer R, et al. Intravenous adminis tration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington’s disease. Proc Natl Acad SciU S A 1994; 91: 9077–80

    CAS  Google Scholar 

  194. Backman C, Rose GM, Bartus RT, et al. Carrier mediated de livery of NGF: alterations in basal forebrain neurons in aged rats revealed using antibodies against low and high affinity NGF receptors. J Comp Neurol 1997; 387: 1–11

    PubMed  CAS  Google Scholar 

  195. Jefferies WA, Brandon MR, Hunt SV, et al. Transferrin receptor on endothelium of brain capillaries. Nature 1984; 312: 162–3

    PubMed  CAS  Google Scholar 

  196. Granholm AC, Biddle PT, Backman C, et al. Peripheral admin istration of nerve growth factor conjugated to an anti-transferrin receptor antibody increases cholinergic survival in intraocular forebrain transplants. In: Flanagan TR, Emerich DF, Winn SR, editors. Methods in neurosciences. Vol. 21. San Diego, CA: Academic Press, 1994: 71–92

    Google Scholar 

  197. Chang TM. Artificial cells in medicine and biotechnology. Appl Biochem Biotechnol 1984; 10: 5–24

    PubMed  CAS  Google Scholar 

  198. Camarata PJ, Suryanarayanan R, Turner DA, et al. Sustained release of nerve growth factor from biodegradable polymer microspheres. Neurosurgery 1992; 30: 313–9

    PubMed  CAS  Google Scholar 

  199. Domb AJ, Ringel I. Polymeric drug carrier systems in the brain. In: Flanagan TR, Emerich DF, Winn SR, editors. Providing pharmacological access to the brain: alternate approaches. San Diego (CA): Academic Press, 1994: 169–83

    Google Scholar 

  200. Powell EM, Sobarzo MR, Saltzman WM. Controlled release of nerve growth factor from a polymeric implant. Brain Res 1990; 515: 309–11

    PubMed  CAS  Google Scholar 

  201. Mendez A, Camarata PJ, Suryanarayanan R, et al. Sustained intracerebral delivery of nerve growth factor with biodegrad able polymer microspheres. In: Flanagan TR, Emerich DF, Winn SR, editors. Providing pharmacological access to the brain: alternate approaches. San Diego (CA): Academic Press, 1994: 150–68

    Google Scholar 

  202. Emerich DF, Winn SR, Harper J, et al. Transplantation of polymer-encapsulated cells genetically modified to secrete human nerve growth factor prevents the loss of degenerating cholinergic neurons in nonhuman primates. J Comp Neurol 1994; 349: 148–64

    PubMed  CAS  Google Scholar 

  203. Kordower JH, Winn SR, Liu YT, et al. The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proc Natl Acad Sci U S A 1994; 91: 10898–902

    PubMed  CAS  Google Scholar 

  204. Emerich DF, Winn SR, Hantraye PM, et al. Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntngton’s disease. Nature 1997; 386: 395–9

    PubMed  CAS  Google Scholar 

  205. Levivier M, Przedborski S, Bencsics C, et al. Intrastriatal im plantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 1995; 15: 7810–20

    PubMed  CAS  Google Scholar 

  206. Frim DM, Uhler TA, Galpern WR, et al. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci U S A 1994; 91: 5104–8

    PubMed  CAS  Google Scholar 

  207. Lucidi-Phillipi CA, Gage FH, Shults CW, et al. Brain-derived neurotrophic factor-transduced fibroblasts: production of BDNF and effects of grafting to the adult rat brain. J Comp Neurol 1995; 354: 361–6

    PubMed  CAS  Google Scholar 

  208. Smith F, Jacoby D, Breakefield XA. Virus vectors for gene delivery to the nervous system. Restor Neurol Neurosci 1995; 8: 21–34

    PubMed  CAS  Google Scholar 

  209. Freese A, Stern M, Kaplitt MG, et al. Prospects for gene therapy in Parkinson’s disease. Mov Disord 1996; 11: 469–88

    PubMed  CAS  Google Scholar 

  210. Horellou P, Mallet J. Gene therapy for parkinson’s disease. Mol Neurobiol 1997; 15: 241–56

    PubMed  CAS  Google Scholar 

  211. Geschwind MD, Lu B, Federoff HJ. Expression of neurotrophic genes from herpes simplex virus type I vectors: modifying neuronal phenotype. In: Flanagan TR, Emerich DF, Winn SR, editors. Providing pharmacological access to the brain: alternate approaches. San Diego, CA: Academic Press, 1994: 462–82

    Google Scholar 

  212. Choi-Lundberg DL, Lin Q, Chang Y-N, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997; 275: 838–41

    PubMed  CAS  Google Scholar 

  213. Lapchak PA, Araujo DM, Hilt DC, et al. Adenoviral vector-mediated GDNF gene therapy in a rodent lesion model of late stage Parkinson’s disease. Brain Res 1997; 777: 153–60

    PubMed  CAS  Google Scholar 

  214. Bilang-Bleuel A, Revah F, Colin P, et al. Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degenera tion and behavioral impairment in a rat model of Parkinson disease. Proc Natl Acad Sci U S A 1997; 94: 8818–23

    PubMed  CAS  Google Scholar 

  215. Choi-Lundberg DL, Lin Q, Schallert T, et al. Behavioral and cellular protection of rat dopaminergic neurons by an adeno viral vector encoding glial cell line-derived neurotrophic fac tor. Exp Neurol 1998; 154: 261–75

    PubMed  CAS  Google Scholar 

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  1. Department of Neurological Sciences, Center for Brain Repair, Rush-Presbyterian St. Luke’s Medical Center, 2242 West Harrison Street, Suite 200, Chicago, Illinois, 60612, USA

    Timothy J. Collier & Caryl E. Sortwell

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Collier, T.J., Sortwell, C.E. Therapeutic Potential of Nerve Growth Factors in Parkinson’s Disease. Drugs & Aging 14, 261–287 (1999). https://doi.org/10.2165/00002512-199914040-00003

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