Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Prospects for new restorative and neuroprotective treatments in Parkinson's disease

Nature volume 399, pages A32–A39 (1999)Cite this article

The degeneration of forebrain dopamine systems in Parkinson's disease has been an effective target for pharmaceutical research over the past four decades. However, although dopamine replacement may alleviate the symptoms of the disease, it does not halt the underlying neuronal degeneration. The past decade has seen major advances in identifying discrete genetic and molecular causes of parkinsonism and mapping the events involved in nigral cell death. This new understanding of the pathogenesis of the disease now offers novel prospects for therapy based on targeted neuroprotection of vulnerable neurons and effective strategies for their replacement.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Lewy bodies in pigmented neurons of the substantia nigra from a PD patient, seen as large spherical inclusions in the cell cytoplasm (arrows).
Figure 2: Rate of progression in Parkinson's disease.
Figure 3
Figure 4: Free radicals in Parkinson's disease.
Figure 5: In vivo imaging of dopaminergic activity in the Parkinsonian basal ganglia shown by [18F]fluorodopa PET.

References

  1. Forno, L. S. in Parkinson's Disease (ed. Stern, G.) 185–238 (Chapman & Hall, London, 1990).

    Google Scholar 

  2. Goedert, M., Jakes, R. & Spillantini, M. G. α-Synuclein and the Lewy body. Neurosci. News 1, 47–52 (1998).

    CAS  Google Scholar 

  3. Olanow, C. W. & Tatton W. G. Etiology and pathogenesis of Parkinson's disease. Annu. Rev. Neurosci. 22, 123–144 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Perl, D. P., Olanow, C. W. & Calne, D. B. Alzheimer's disease and Parkinson's disease; distinct entities or extremes of a spectrum of neurodegeneration? Ann. Neurol. (suppl.) 44, s19–S31 (1998).

    Article  CAS  Google Scholar 

  5. Gasser, T. Genetics of Parkinson's disease. Ann. Neurol. 44, s53–S57 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Tanner, C. M. et al. Parkinson's disease in twins: an etiologic study. J. Am. Med. Assoc. 281, 341–346 (1999).

    Article  CAS  Google Scholar 

  7. Brooks, D. J. The early diagnosis of Parkinson's disease. Ann. Neurol. (suppl.) 44, S10–S18 (1998).

    Article  CAS  Google Scholar 

  8. Langston, J. W. Epidemiology versus genetics in Parkinson's disease: progress in resolving an age-old debate. Ann. Neurol. (suppl.) 44, S45–S52 (1998).

    Article  CAS  Google Scholar 

  9. Spillantini, M. G. et al. α-Synuclein in Lewy bodies. Nature 388, 839–890 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Mezey, E. et al. α-Synuclein in neurodegenerative disorders: murderer or accomplice? Nature Med. 4, 755–757 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Conway, K. A., Harper, J. D. & Lansbury, P. T., Accelerated in vitro fibril formation by a mutant asynuclein linked to early onset Parkinson's disease. Nature Med. 4, 1318–1320 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Poewe, W. & Granata, R. . in Movement Disorders. Neurological Principles and Practice (eds Watts, R. L. & Koller, W. C.) 201–219 (McGraw-Hill, New York, 1997).

    Google Scholar 

  13. Marsden, C. D. & Parkes, J. D. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1, 345–349 (1977).

    Article  CAS  PubMed  Google Scholar 

  14. Marsden, C. D., Linazasoro, G. & Obeso, J. A. An introduction to the new surgery for Parkinson's disease: past and present problems. Adv. Neurol. 74, 143–147 (1997).

    CAS  PubMed  Google Scholar 

  15. DeLong, M. R. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 13, 281–285 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. Starr, P. A., Vitek, J. L. & Bakay, R. A. E. Ablative surgery and deep brain stimulation for Parkinson's disease. Neurosurgery 43, 989–1013 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Pollak, P., Benabid, A. L., Limousin, P. & Benazzouz, A. Chronic intracerebral stimulation in Parkinson's disease. Adv. Neurol. 74, 213–220 (1997).

    CAS  PubMed  Google Scholar 

  18. Bernheimer, H., Birkmayer Hornykiewicz, O., Jellinger, K. & Seitelberger, F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. Neurol. Sci. 20, 415–455 (1973).

    Article  CAS  PubMed  Google Scholar 

  19. Fearnley, J. & Lees, A. J. Parkinson's disease: neuropathology. Brain 114, 2283–2301 (1991).

    Article  PubMed  Google Scholar 

  20. McGeer, P. L., Itagaki, S., Akiyama, H. & McGeer, E. G. Rate of cell death in parkinsonism indicates active neuropathological process. Ann. Neurol. 24, 574–576 (1989).

    Article  Google Scholar 

  21. Calne, D. B. & Langston, J. W. Aetiology of Parkinson's disease. Lancet 2, 1457–1459 (1983).

    Article  CAS  PubMed  Google Scholar 

  22. Olanow, C. W., Jenner, P. & Beal, M. F. Cell death and neuroprotection in Parkinson's disease. Ann. Neurol. (suppl.) 44, S1–S196 (1998).

    Article  Google Scholar 

  23. Mizuno, Y. et al. in Movement Disorders. Neurological Principles and Practice (eds Watts, R. L. & Koller, W. C.) 161–182 (McGraw-Hill, New York, 1997).

    Google Scholar 

  24. Jenner, P. & Olanow, C. W. Understanding cell death in Parkinson's disease. Ann. Neurol. (suppl.) 44, S72–S84 (1998).

    Article  CAS  Google Scholar 

  25. Ebadi, M., Srinivasan, S. K. & Baxi, M. D. Oxidative stress and antioxidant therapy in Parkinson's disease. Prog. Neurobiol. 48, 1–19 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Schapira, A. H. V., Cooper, J. M. & Dexter, D. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1, 1269 (1989).

    Article  CAS  PubMed  Google Scholar 

  27. Burke, R. E. & Kholodilov, N. G. Programmed cell death: does it play a role in Parkinson's disease? Ann. Neurol. (suppl.) 44, S126–S133 (1998).

    Article  CAS  Google Scholar 

  28. Tatton, N. A., Maclean-Fraser, A., Tatton, W. G., Perl, D. P. & Olanow, C. W. A fluorescent doublelabeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann. Neurol. (suppl.) 44, S142–S148 (1998).

    Article  CAS  Google Scholar 

  29. Marsden, C. D. & Olanow, C. W. The causes of Parkinson's disease are being unraveled and rational neuroprotective therapy is close to reality. Ann. Neurol. (suppl.) 44, S189–S196 (1998).

    Article  CAS  Google Scholar 

  30. Shoulson, I. et al.Mortality in DATATOP: a multicenter trial in early Parkinson's disease. Ann. Neurol. 43, 318–325 (1998).

    Article  Google Scholar 

  31. Koller, W. C. Neuroprotection for Parkinson's disease. Ann. Neurol. (suppl.) 44, S155–S159 (1998).

    Article  CAS  Google Scholar 

  32. Olanow, C. W., Jenner, P. & Brooks, D. Dopamine agonists and neuroprotection in Parkinson's disease. Ann. Neurol. (suppl.) 44, S167–S174 (1998).

    Article  CAS  Google Scholar 

  33. Rodriguez, M. C., Obeso, J. & Olanow, C. W. Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann. Neurol. (suppl.) 44, S175–S188 (1998).

    Article  CAS  Google Scholar 

  34. Hagg, T. Neurotrophins prevent death and differentially affect tyrosine hydroxylase of adult rat nigrostriatal neurons in vivo. Exp. Neurol. 149, 183–192 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Unsicker, K., Suter-Crazzolara, C. & Krieglstein, K. Growth factor function in the development and maintenance of midbrain dopaminergic neurons: concepts, facts and prospects for TGF-β. Ciba Found. Symp. 196, 70–80 (1996).

    CAS  PubMed  Google Scholar 

  36. Gash, D. M., Zhang, Z. M. & Gerhardt, G. Neuroprotective and neurorestorative properties of GDNF. Ann. Neurol. (suppl) 44, S121–S125 (1998).

    Article  CAS  Google Scholar 

  37. Björklund, A., Rosenblad, C., Winkler, C. & Kirik, D. Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. Neurobiol. Dis. 4, 186–200 (1997).

    Article  PubMed  Google Scholar 

  38. Palfi, S. et al. Clinical and pathological evaluation of patient with Parkinson's disease (PD) following intracerebroventricular (icv) GDNF. Soc. Neurosci. Abstr. 24, 41 (1998).

    Google Scholar 

  39. Snyder, S. H. et al. Neural actions of immunophilin ligands. Trends Pharmacol. Sci. 19, 21–26 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Steiner, J. P., Hamilton, G. S., Ross, D. T. & Valentine, H. L. Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. Proc. Natl Acad. Sci USA 94, 2019–2124 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Constantini, L. C. 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. 5, 97–106 (1998).

    Article  Google Scholar 

  42. Green, D. R. & Reed, J. C. Mitochondria and apoptosis. Science 281, 1309–1312 (1999).

    Article  Google Scholar 

  43. Schierle, G. S. et al. Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nature Med. 5, 97–100 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Dunnett, S. B. & Björklund, A. Functional Neural Transplantation (Raven, New York, 1994).

  45. Lindvall, O. Neural transplantation: a hope for patientswith Parkinson's disease? NeuroReport 8, iiix (1997).

    Article  Google Scholar 

  46. Olanow, C. W., Freeman, T. B. & Kordower, J. H. Neural transplantation as a therapy for Parkinson's disease. Adv. Neurol. 74, 249–269 (1997).

    CAS  PubMed  Google Scholar 

  47. Wenning, G. K. et al. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann. Neurol. 42, 95–107 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Kordower, J. H., Freeman, T. B. & Olanow, C. W. Neuropathology of fetal nigral grafts in patients with Parkinson's disease. Mov. Dis. 13, 88–95 (1998).

    Article  Google Scholar 

  49. Kordower, J. H. et al. Fetal grafting for Parkinson's disease: expression of immune markers in two patients with functional fetal nigral implants. Cell Transplant. 6, 213–219 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Boer, G. J. Ethical guidelines for the use of human embryonic or fetal tissue for experimental and clinical neurotransplantation and research. J. Neurol. 242, 113 (1994).

    Article  Google Scholar 

  51. Kordower, J. H., Goetz, C. G., Freeman, T. B. & Olanow, C. W. Dopaminergic transplants in patients with Parkinson's disease: neuroanatomical correlates of clinical recovery. Exp. Neurol. 144, 41–46 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Zawada, W. M. et al. Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats. Brain Res. 786, 96–103 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Sinclair, S. R., Svendsen, C. N., Torres, E. M., Fawcett, J. W. & Dunnett, S. B. The effects of glial cell linederived neurotrophic factor (GDNF) on embryonic nigral grafts. NeuroReport 7, 2547–2552 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Rosenblad, C., Martinez-Serrano, A. & Bjβrklund, A. Glial cell line-derived neurotrophic factor increases survival, growth and function of intrastriatal fetal nigral dopaminergic grafts. Neuroscience 75, 979–985 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Yurek, M. Glial cell line-derived neurotrophic factor improves survival of dopaminergic neurons in transplants of fetal ventral mesencephalic tissue. Exp. Neurol. 153, 195–202 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Pakzaban, P. & Isacson, O. Neural xenotransplantation: reconstruction of neuronal circuitry across species barriers. Neuroscience 62, 989–1001 (1994).

    Article  CAS  PubMed  Google Scholar 

  57. Isacson, O. & Breakefield, X. O. Benefits and risks of hosting animal cells in the human brain. Nature Med. 3, 964–969 (1997).

    Article  CAS  PubMed  Google Scholar 

  58. Deacon, T. et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nature Med. 3, 350–353 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Butler, D. Last chance to stop and think on risks of xenotransplants. Nature 391, 320–324 (1998).

    ADS  CAS  PubMed  Google Scholar 

  60. Mayer, E., Dunnett, S. B. & Fawcett, J. W. Mitogenic effect of basic fibroblast growth factor on embryonic ventral mesencephalic dopaminergic neurone precursors. Dev. Brain. Res. 72, 253–258 (1993).

    Article  CAS  Google Scholar 

  61. Bouvier, M. M. & Mytilineou, C. Basic fibroblast growth factor increases division and delays differentiation of dopamine precursors in vitro. J. Neurosci. 15, 7141–7149 (1995).

    Article  CAS  PubMed  Google Scholar 

  62. Studer, L., Tabar, V. & McKay, R. D. G. Transplantaton of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nature Neurosci. 1, 290–295 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Ling, Z. D., Potter, E. D., Lipton, J. W. & Carvey, P. M. Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp. Neurol. 149, 411–423 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Ye, W. L., Shimamura, K., Rubenstein, J. L. R., Hynes, M. A. & Rosenthal, A. FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93, 755–766 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. Brundin, P., Duan, W. -M. & Sauer, H. . in Functional Neural Transplantation (eds Dunnett, S. B. & Björklund, A.) 9–46 (Raven, New York, 1994).

    Google Scholar 

  66. Goetz, C. G. et al. United Parkinson Foundation neurotransplantation registry on adrenal medullary transplants: presurgical, and 1-year and 2-year follow up. Neurology 41, 1719–1722 (1991).

    Article  CAS  PubMed  Google Scholar 

  67. Winn, S. R. L., Tresco, P. A. & Aebischer, P. An encapsulated dopamine-releasing polymer alleviates experimental parkinsonism in rats. Exp. Neurol. 105, 244–250 (1989).

    Article  CAS  PubMed  Google Scholar 

  68. Becker, J. B. et al. Sustained behavioral recovery from unilateral nigrostriatal damage produced by the controlled release of dopamine from a silicone polymer pellet placed into the denervated striatum. Brain Res. 508, 60–64 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  69. Aebischer, P., Goddard, M., Signore, A. P. & Timpson, R. L. Functional recovery in hemiparkinsonian primates transplanted with polymer-encapsulated PC12 cells. Exp. Neurol. 126, 151–158 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Emerich, D. F. et al. Polymer-encapsulated PC12 cells promote recovery of motor function in aged rats. Exp. Neurol. 122, 37–47 (1993).

    Article  CAS  PubMed  Google Scholar 

  71. Espejo, E. F., Montoro, R. J., Armengol, J. A. & López-Barneo, J. Cellular and functional recovery of Parkinsonian rats after intrastriatal transplantaton of carotid body cell aggregates. Neuron 20, 197–206 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Fisher, L. J., Jinnah, H. A., Kale, L. C., Higgins, G. A. & Gage, F. H. Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-DOPA. Neuron 6, 371–380 (1991).

    Article  CAS  PubMed  Google Scholar 

  73. Lundberg, C., Horellou, P., Mallet, J. & Björklund, A. Generation of DOPA-producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene: in vitro characterisation and in vivo effects in the rat Parkinson model. Exp. Neurol. 139, 39–53 (1996).

    Article  CAS  PubMed  Google Scholar 

  74. Anton, R. et al. Neural-targeted gene therapy for rodent and primate hemiparkinsonism. Exp. Neurol. 127, 207–218 (1994).

    Article  CAS  PubMed  Google Scholar 

  75. Chase, T. N. et al. Rationale for continuous dopaminomimetic therapy of Parkinson's disease. Neurology 39, 710 (1989).

    Google Scholar 

  76. Raymon, H. K., Thode, S. & Gage, F. H. Application of ex vivo gene therapy in the treatment of Parkinson's disease. Exp. Neurol. 144, 82–91 (1997).

    Article  CAS  PubMed  Google Scholar 

  77. Kang, U. J. Potential of gene therapy for Parkinson's disease: neurobiologic issues and new developments in gene transfer methodologies. Mov. Dis. 13, 59–72 (1998).

    Google Scholar 

  78. Bencsics, C. et al. Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts. J. Neurosci. 16, 4449–4456 (1996).

    Article  CAS  PubMed  Google Scholar 

  79. Leff, S. E., Rendahl, K. G., Spratt, S. K., Kang, U. J. & Mandel, R. J. In vivo L-DOPA production by genetically modified primary rat fibroblast or 9L gliosarcoma cell grafts via coexpression of GTP cyclohydrolase I with tyrosine hydroxylase. Exp. Neurol. 151, 249–264 (1998).

    Article  CAS  PubMed  Google Scholar 

  80. Barker, R. A. S. B. Ibotenic acid lesions of the striatum reduce drug-induced rotation in the 6-hydroxydopamine-lesioned rat. Exp. Brain Res. 101, 365–374 (1994).

    Article  CAS  PubMed  Google Scholar 

  81. Isacson, O. Behavioral effects and gene delivery in a rat model of Parkinson's disease. Science 269, 856–856 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  82. Frim, D. M. 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. Nat Acad. Sci. USA 91, 5104–5108 (1999).

    Article  ADS  Google Scholar 

  83. Levivier, M., Przedborski, S., Bencsics, C. & Kang, U. J. Intrastriatal implantation 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. 15, 7810–7820 (1995).

    Article  CAS  PubMed  Google Scholar 

  84. Tseng, J. L., Baetge, E. E., Zurn, A. D. & Aebischer, P. GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J Neurosci. 17, 325–333 (1997).

    Article  CAS  PubMed  Google Scholar 

  85. Choi-Lundberg, D. L. et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275, 838–841 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Mandel, R. J., Spratt, S. K., Snyder, R. O. & Leff, S. E. Midbrain injection of recombinant adenoassociated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats. Proc. Natl Acad. Sci. USA 94, 14083–14088 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  87. Bilang-Bleuel, A. et al. Intrastriatal injection of an adenoviral vector expressing glial cell line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson's disease. Proc. Natl Acad. Sci. USA 94, 8818–8823 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  88. Choi-Lundberg, D. L. et al. Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor. Exp. Neurol. 154, 261–275 (1998).

    Article  CAS  PubMed  Google Scholar 

  89. Blömer, U., Kafri, T., Randolph-Moore, L., Verma, I. M. & Gage, F. H. Bcl-xL protects adult septal cholinergic neurons from axotomized cell death. Proc. Natl Acad. Sci. USA 95, 2603–2608 (1998).

    Article  ADS  PubMed  Google Scholar 

  90. Jordan, J. et al. Expression of human copper/zinc-superoxide dismutase inhibits the death of rat sympathetic neurons caused by withdrawal of nerve growth-factor. Mol. Pharmacol. 47, 1095–1100 (1995).

    CAS  PubMed  Google Scholar 

  91. Morrish, P. K., Sawle, G. V. & Brooks, D. J. An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. Brain 119, 585–591 (1996).

    Article  PubMed  Google Scholar 

  92. Olanow, C. W. & Arendash, G. W. Metals and free radicals in neurodegeneration. Curr. Opin. Neurol. 7, 548–558 (1994).

    Article  CAS  PubMed  Google Scholar 

  93. Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997).

    Article  CAS  PubMed  Google Scholar 

  94. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  95. Leroy, M. et al. The ubiquitin pathway in Parkinson's disease. Nature 395, 451–452 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  96. Farrer, M. et al. Low frequency of α-synuclein mutations in familial Parkinson's disease. Ann. Neurol. 43, 394–397 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  97. Gasser, T. et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nature Genet. 18, 262–265 (1998).

    Article  CAS  PubMed  Google Scholar 

  98. Kruger, R. et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nature Genet. 18, 106–108 (1998).

    Article  CAS  PubMed  Google Scholar 

  99. Owen, A. M., Sahakian, B. J. & Robbins, T. W. . in Memory in Neurodegenerative Disease: Biological, Cognitive and Clinical Perspectives (ed. Trosyter, A. I.) 157–171 (Cambridge Univ. Press, Cambridge, 1998).

    Book  Google Scholar 

Download references

Acknowledgements

We thank R. A. Barker, P. Brundin, R. Castilho, O. Lindvall, D. Menon, A. E. Rosser, M. G. Spillantini and C. Watts for helpful comments and discussion during preparation of the manuscript.

Author information

Authors and Affiliations

  1. Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK

    Stephen B. Dunnett

  2. Wallenberg Neuroscience Center, Lund University, Sölvegatan 17, Lund, S-22362, Sweden

    Anders Björklund

Authors
  1. Stephen B. Dunnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anders Björklund
    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

Dunnett, S., Björklund, A. Prospects for new restorative and neuroprotective treatments in Parkinson's disease. Nature 399, A32–A39 (1999). https://doi.org/10.1038/399a032

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/399a032

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing