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The role of α-synuclein in Parkinson's disease: insights from animal models

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Abstract

The abnormal accumulations of fibrillar α-synuclein in Lewy bodies and the mutations in the gene for α-synuclein in familial forms of Parkinson's disease have led to the belief that this protein has a central role in a group of neurodegenerative diseases known as the synucleinopathies. Our understanding of the biology of α-synuclein has increased significantly since its discovery in 1997, and recently developed animal models of the synucleinopathies have contributed to this understanding. The information gleaned from animal models has the potential to provide a framework for continuing the development of rational therapeutic strategies.

Key Points

  • Since the discovery that mutations in α-synuclein can cause familial Parkinson's disease, there has been great interest in its role in the pathogenesis of the disease. Other genes that have been implicated in familial Parkinson's disease might also influence the structure or clearance of α-synuclein. In Parkinson's disease and other disorders, α-synuclein is found in intraneuronal inclusions called Lewy bodies, and it is proposed that α-synuclein forms oligomers and fibrils before aggregating into Lewy bodies. However, it is unclear whether α-synuclein oligomers, fibrils or Lewy bodies are protective or toxic to neurons.

  • Interactions between certain α-synuclein conformations and dopamine metabolism might cause selective degeneration of dopamine neurons, as is observed in Parkinson's disease. Dopamine metabolism generates reactive oxygen species, which might accelerate aggregation of α-synuclein, which itself might increase the generation of toxic reactive oxygen species.

  • Both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone are used to generate animal models of Parkinson's disease. MPTP is converted to MPP+, which causes neurodegeneration by entering dopamine neurons through the dopamine transporter and inhibiting mitochondrial complex I. Mice lacking α-synuclein are resistant to the effects of MPTP, and it has been proposed that the increase in reactive oxygen species caused by MPP+ leads to an increase in α-synuclein aggregation which further increases the generation of reactive oxygen species. MPTP does not, however, cause Lewy body formation.

  • Rotenone is also an inhibitor of mitochondrial complex I, although it enters the cell through a different route to MPP+, and α-synuclein knockout mice are not resistant to its effects. Rats treated with rotenone show nigrostriatal degeneration accompanied by a variety of motor symptoms, and develop Lewy body-like inclusions.

  • Overexpression of normal or mutant human α-synuclein in non-rodent species can generate genetic models of Parkinson's disease. In flies, which contain no endogenous α-synuclein, α-synuclein expression causes age-related depletion of dopamine neurons. This is proposed to be related to the abnormal aggregation of α-synuclein, and can be prevented by concomitant expression of a molecular chaperone.

  • Various promoters and α-synuclein transgenes have been used to generate α-synuclein transgenic mice, with variable results. None of the transgenic mice show a true parkinsonian condition that includes Lewy bodies, but some do exhibit loss of dopamine neurons and motor impairments. It is possible that higher and more consistent levels of transgene expression will be needed to create a more useful transgenic mouse model.

  • Viral vectors have been used to introduce α-synuclein into the brains of rats and monkeys. Again, the results have been variable but this system might also prove useful if expression can be optimized.

  • No existing animal model shows the full spectrum of features of Parkinson's disease, although the models that do exist complement each other. Continued development of these models should allow studies that elucidate further the pathogenesis of Parkinson's disease, and improve our understanding of the role of α-synuclein in both health and disease.

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References

  1. 1

    Polymeropoulos, M. H. et al. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997). The first report showing that a missense mutation in the α-synuclein gene (A53T) causes an early-onset, familial form of PD. This was the first study to identify a genetic cause of PD.

  2. 2

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

  3. 3

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

  4. 4

    Bonifati, V. et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256–259 (2003).

  5. 5

    Mouradian, M. M. Recent advances in the genetics and pathogenesis of Parkinson disease. Neurology 58, 179–185 (2002).

  6. 6

    Shimura, H. et al. Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson's disease. Science 293, 263–269 (2001).

  7. 7

    Liu, Y., Fallon, L., Lashuel, H. A., Liu, Z. & Lansbury, P. T. Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson's disease susceptibility. Cell 111, 209–218 (2002).

  8. 8

    Miller, D. W. et al. L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin–proteasome system. J. Biol. Chem. 2003 Jul 8 (DOI: 10.1074/jbc.M304272200).

  9. 9

    Mitsumoto, A. & Nakagawa, Y. DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radic. Res. 35, 885–893 (2001).

  10. 10

    Mitsumoto, A. et al. Oxidized forms of peroxiredoxins and DJ-1 on two-dimensional gels increased in response to sublethal levels of paraquat. Free Radic. Res. 35, 301–310 (2001).

  11. 11

    Wilson, M. A., Collins, J. L., Hod, Y., Ringe, D. & Petsko, G. A. The 1.1-Å resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease. Proc. Natl Acad. Sci. USA 100, 9256–9261 (2003).

  12. 12

    Spillantini, M. G. et al. α-Synuclein in Lewy bodies. Nature 388, 839–840 (1997). The first study to demonstrate the presence of α-synuclein in the Lewy bodies and Lewy neurites of patients with idiopathic PD and Lewy body dementia.

  13. 13

    Wakabayashi, K. et al. Synphilin-1 is present in Lewy bodies in Parkinson's disease. Ann. Neurol. 47, 521–523 (2000).

  14. 14

    Schlossmacher, M. G. et al. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am. J. Pathol. 160, 1655–1667 (2002).

  15. 15

    Kawamoto, Y. et al. 14-3-3 proteins in Lewy bodies in Parkinson disease and diffuse Lewy body disease brains. J. Neuropathol. Exp. Neurol. 61, 245–253 (2002).

  16. 16

    Yamazaki, M. et al. α-Synuclein inclusions in amygdala in the brains of patients with the parkinsonism–dementia complex of Guam. J. Neuropathol. Exp. Neurol. 59, 585–591 (2000).

  17. 17

    Baba, M. et al. Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884 (1998).

  18. 18

    Gai, W. P. et al. α-Synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy. Exp. Neurol. 181, 68–78 (2003).

  19. 19

    Conway, K. A., Harper, J. D. & Lansbury, P. T. Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease. Nature Med. 4, 1318–1320 (1998). This work described the formation of α-synuclein protofibrils and fibrils during the process of fibrillization. A53T α-synuclein mutant protein was shown to fibrillize faster than wild-type protein.

  20. 20

    Wood, S. J. et al. α-Synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. J. Biol. Chem. 274, 19509–19512 (1999).

  21. 21

    El-Agnaf, O. M. et al. Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments. FEBS Lett. 440, 71–75 (1998).

  22. 22

    Giasson, B. I. & Lee, V. M. Parkin and the molecular pathways of Parkinson's disease. Neuron 31, 885–888 (2001).

  23. 23

    Conway, K. A. et al. Accelerated oligomerization by Parkinson's disease linked α-synuclein mutants. Ann. NY Acad. Sci. 920, 42–45 (2000).

  24. 24

    Conway, K. A. et al. Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc. Natl Acad. Sci. USA 97, 571–576 (2000). This seminal study indicated that both α-synuclein mutations responsible for familial PD increase the rate of protofibril formation during the process of fibrillization.

  25. 25

    Volles, M. J. & Lansbury, P. T. Jr. Vesicle permeabilization by protofibrillar α-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41, 4595–4602 (2002). This paper demonstrated that α-synuclein protofibrils can permeabilize vesicles in vitro , leading to the release of small cytoplasmic molecules such as DA.

  26. 26

    Lashuel, H. A., Hartley, D., Petre, B. M., Walz, T. & Lansbury, P. T. Jr. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418, 291 (2002).

  27. 27

    Xu, J. et al. Dopamine-dependent neurotoxicity of α-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nature Med. 8, 600–606 (2002).

  28. 28

    Lo Bianco, C., Ridet, J. L., Schneider, B. L., Deglon, N. & Aebischer, P. α-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc. Natl Acad. Sci. USA 99, 10813–10818 (2002).

  29. 29

    Ostrerova-Golts, N. et al. The A53T α-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20, 6048–6054 (2000).

  30. 30

    Kim, K. S. et al. The ceruloplasmin and hydrogen peroxide system induces α-synuclein aggregation in vitro. Biochimie 84, 625–631 (2002).

  31. 31

    Junn, E. & Mouradian, M. M. Human α-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci. Lett. 320, 146–150 (2002).

  32. 32

    Tabner, B. J., Turnbull, S., El-Agnaf, O. M. & Allsop, D. Formation of hydrogen peroxide and hydroxyl radicals from A(β) and α-synuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease. Free Radic. Biol. Med. 32, 1076–1083 (2002).

  33. 33

    George, J. M., Jin, H., Woods, W. S. & Clayton, D. F. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15, 361–372 (1995).

  34. 34

    Quilty, M. C., Gai, W. P., Pountney, D. L., West, A. K. & Vickers, J. C. Localization of α-, β-, and γ-synuclein during neuronal development and alterations associated with the neuronal response to axonal trauma. Exp. Neurol. 182, 195–207 (2003).

  35. 35

    Abeliovich, A. et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239–252 (2000). The first study to create α-synuclein-knockout mice, showing that α-synuclein deletion only led to slight changes in synaptic transmission.

  36. 36

    Cabin, D. E. et al. Synaptic vesicle depletion with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking α-synuclein. J. Neurosci. 22, 8797–8807 (2002).

  37. 37

    Perez, R. G. et al. A role for α-synuclein in the regulation of dopamine biosynthesis. J. Neurosci. 22, 3090–3099 (2002).

  38. 38

    Dauer, W. et al. Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP. Proc. Natl Acad. Sci. USA 99, 14524–14529 (2002). These authors were the first to show that α-synuclein- knockout mice, and neuronal cultures derived from these mice, are resistant to the neurotoxin MPTP.

  39. 39

    Schluter, O. M. et al. Role of α-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience 118, 985–1002 (2003).

  40. 40

    Fearnley, J. M. & Lees, A. J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 114, 2283–2301 (1991).

  41. 41

    Marsden, C. D. Problems with long-term levodopa therapy for Parkinson's disease. Clin. Neuropharmacol. 17, S32–S44 (1994).

  42. 42

    Dawson, T. M. & Dawson, V. L. Neuroprotective and neurorestorative strategies for Parkinson's disease. Nature Neurosci. 5, S1058–S1061 (2002).

  43. 43

    Langston, J. W., Ballard, P., Tetrud, J. W. & Irwin, I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979–980 (1983).

  44. 44

    Cardellach, F. et al. Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease. Neurology 43, 2258–2262 (1993).

  45. 45

    Blin, O. et al. Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy. J. Neurol. Sci. 125, 95–101 (1994).

  46. 46

    Owen, A. D., Schapira, A. H., Jenner, P. & Marsden, C. D. Indices of oxidative stress in Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies. J. Neural Transm. Suppl. 51, 167–173 (1997).

  47. 47

    Liu, Y., Fiskum, G. & Schubert, D. Generation of reactive oxygen species by the mitochondrial electron transport chain. J. Neurochem. 80, 780–787 (2002).

  48. 48

    Kang, J. H. & Kim, K. S. Enhanced oligomerization of the α-synuclein mutant by the Cu,Zn-superoxide dismutase and hydrogen peroxide system. Mol. Cells 15, 87–93 (2003).

  49. 49

    Forno, L. S., DeLanney, L. E., Irwin, I. & Langston, J. W. Electron microscopy of Lewy bodies in the amygdala–parahippocampal region. Comparison with inclusion bodies in the MPTP-treated squirrel monkey. Adv. Neurol. 69, 217–228 (1996).

  50. 50

    Spillantini, M. G. et al. Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neurosci. Lett. 251, 205–208 (1998).

  51. 51

    Kowall, N. W. et al. MPTP induces α-synuclein aggregation in the substantia nigra of baboons. Neuroreport 11, 211–213 (2000).

  52. 52

    Vila, M., Wu, D. C. & Przedborski, S. Engineered modeling and the secrets of Parkinson's disease. Trends Neurosci. 24, S49–S55 (2001).

  53. 53

    Kuhn, K. et al. The mouse MPTP model: gene expression changes in dopaminergic neurons. Eur. J. Neurosci. 17, 1–12 (2003).

  54. 54

    Beal, M. F. Experimental models of Parkinson's disease. Nature Rev. Neurosci. 2, 325–334 (2001).

  55. 55

    Meredith, G. E. et al. Lysosomal malfunction accompanies α-synuclein aggregation in a progressive mouse model of Parkinson's disease. Brain Res. 956, 156–165 (2002).

  56. 56

    Neystat, M. et al. α-Synuclein expression in substantia nigra and cortex in Parkinson's disease. Mov. Disord. 14, 417–422 (1999).

  57. 57

    Gorell, J. M., Johnson, C. C., Rybicki, B. A., Peterson, E. L. & Richardson, R. J. The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living. Neurology 50, 1346–1350 (1998).

  58. 58

    Menegon, A., Board, P. G., Blackburn, A. C., Mellick, G. D. & Le Couteur, D. G. Parkinson's disease, pesticides, and glutathione transferase polymorphisms. Lancet 352, 1344–1346 (1998).

  59. 59

    Hensley, K. et al. Interaction of α-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site. J. Neurochem. 71, 2549–2557 (1998).

  60. 60

    Seaton, T. A., Cooper, J. M. & Schapira, A. H. Free radical scavengers protect dopaminergic cell lines from apoptosis induced by complex I inhibitors. Brain Res. 777, 110–118 (1997).

  61. 61

    Betarbet, R., Sherer, T. B. & Greenamyre, J. T. Animal models of Parkinson's disease. Bioessays 24, 308–318 (2002).

  62. 62

    Betarbet, R. et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci. 3, 1301–1306 (2000). This study described the rotenone rat model of PD. These animals showed nigrostriatal system degeneration, Lewy-like inclusion bodies and motor impairment.

  63. 63

    Masliah, E. et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287, 1265–1269 (2000). These authors were the first to develop α-synuclein transgenic mice. These mice were created using the PDGFβ promoter, and exhibited a loss of striatal dopaminergic terminals.

  64. 64

    Auluck, P. K. & Bonini, N. M. Pharmacological prevention of Parkinson disease in Drosophila. Nature Med. 8, 1185–1186 (2002).

  65. 65

    Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000). The first published example of α-synuclein Drosophila transgenics. The wild-type and mutant (A53T and A30P) α-synuclein transgenic flies exhibited DA neuron loss and neuronal inclusions resembling Lewy bodies.

  66. 66

    Takahashi, M. et al. Phosphorylation of α-synuclein characteristic of synucleinopathy lesions is recapitulated in α-synuclein transgenic Drosophila. Neurosci. Lett. 336, 155–158 (2003).

  67. 67

    Pendleton, R. G., Parvez, F., Sayed, M. & Hillman, R. Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster. J. Pharmacol. Exp. Ther. 300, 91–96 (2002).

  68. 68

    Fujiwara, H. et al. α-Synuclein is phosphorylated in synucleinopathy lesions. Nature Cell Biol. 4, 160–164 (2002).

  69. 69

    Kahle, P. J. et al. Selective insolubility of α-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am. J. Pathol. 159, 2215–2225 (2001).

  70. 70

    Warrick, J. M. et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genet. 23, 425–428 (1999).

  71. 71

    Bonini, N. M. Chaperoning brain degeneration. Proc. Natl Acad. Sci. USA 99, S16407–S16411 (2002).

  72. 72

    Yang, Y., Nishimura, I., Imai, Y., Takahashi, R. & Lu, B. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37, 911–924 (2003).

  73. 73

    Greene, J. C. et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl Acad. Sci. USA 100, 4078–4083 (2003). The first deletion of the parkin gene in Drosophila . The parkin-null flies exhibited muscle degeneration but no defects in the dopaminergic system.

  74. 74

    Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

  75. 75

    Sturchler-Pierrat, C. et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl Acad. Sci. USA 94, 13287–13292 (1997).

  76. 76

    Wiessner, C. et al. Neuron-specific transgene expression of Bcl-X L but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice. Neurosci. Lett. 268, 119–122 (1999).

  77. 77

    van der Putten, H. et al. Neuropathology in mice expressing human α-synuclein. J. Neurosci. 20, 6021–6029 (2000).

  78. 78

    Kahle, P. J., Neumann, M., Ozmen, L. & Haass, C. Physiology and pathophysiology of α-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated protein. Ann. NY Acad. Sci. 920, 33–41 (2000).

  79. 79

    Matsuoka, Y. et al. Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter. Neurobiol. Dis. 8, 535–539 (2001).

  80. 80

    Rathke-Hartlieb, S. et al. Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant α-synuclein transgenic mice. J. Neurochem. 77, 1181–1184 (2001).

  81. 81

    Richfield, E. K. et al. Behavioral and neurochemical effects of wild-type and mutated human α-synuclein in transgenic mice. Exp. Neurol. 175, 35–48 (2002).

  82. 82

    Giasson, B. I. et al. Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 34, 521–533 (2002).

  83. 83

    Lee, M. K. et al. Human α-synuclein-harboring familial Parkinson's disease-linked Ala-53→Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice. Proc. Natl Acad. Sci. USA 99, 8968–8973 (2002).

  84. 84

    Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M. & Masliah, E. β-Synuclein inhibits α-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron 32, 213–223 (2001).

  85. 85

    Park, J. Y. & Lansbury, P. T. Jr. β-Synuclein inhibits formation of α-synuclein protofibrils: a possible therapeutic strategy against Parkinson's disease. Biochemistry 42, 3696–3700 (2003).

  86. 86

    Klein, R. L., King, M. A., Hamby, M. E. & Meyer, E. M. Dopaminergic cell loss induced by human A30P α-synuclein gene transfer to the rat substantia nigra. Hum. Gene Ther. 13, 605–612 (2002).

  87. 87

    Kirik, D. et al. Parkinson-like neurodegeneration induced by targeted overexpression of α-synuclein in the nigrostriatal system. J. Neurosci. 22, 2780–2791 (2002).

  88. 88

    Rochet, J. C., Conway, K. A. & Lansbury, P. T. Jr. Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse α-synuclein. Biochemistry 39, 10619–10626 (2000).

  89. 89

    Kirik, D. et al. Nigrostriatal α-synucleinopathy induced by viral vector-mediated overexpression of human α-synuclein: a new primate model of Parkinson's disease. Proc. Natl Acad. Sci. USA 100, 2884–2889 (2003). The first study attempting to create a primate model overexpressing the α-synuclein gene. These primates exhibited nigrostriatal degeneration, but lacked a motor phenotype resembling PD.

  90. 90

    Uversky, V. N. & Fink, A. L. Amino acid determinants of α-synuclein aggregation: putting together pieces of the puzzle. FEBS Lett. 522, 9–13 (2002).

  91. 91

    Couzin, J. Parkinson's disease. Dopamine may sustain toxic protein. Science 294, 1257–1258 (2001).

  92. 92

    Hishikawa, N., Hashizume, Y., Yoshida, M. & Sobue, G. Clinical and neuropathological correlates of Lewy body disease. Acta Neuropathol. (Berl.) 105, 341–350 (2003).

  93. 93

    Conway, K. A., Rochet, J. C., Bieganski, R. M. & Lansbury, P. T. Jr. Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct. Science 294, 1346–1349 (2001). This prominent work showed that DA stabilizes the protofibrillary conformation of α-synuclein.

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Correspondence to Kathy Steece-Collier.

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Glossary

MISSENSE MUTATION

A mutation that results in the substitution of an amino acid in a protein.

PENETRANCE

The probability that an individual with a particular genotype manifests a given phenotype. Complete penetrance corresponds to the situation in which every individual with the same specific genotype manifests the phenotype in question.

ROTAROD TEST

Motor test that probes the ability of rodents to keep their balance on a cylinder that rotates continuously at a slow speed, commonly 5–6 revolutions per minute.

ADENO-ASSOCIATED VIRUSES

A group of viruses that require co-infection with an adenovirus or a herpesvirus for their replication. If no helper virus is present, the genome of adeno-associated viruses can be integrated into the host DNA, resulting in latent infection.

LENTIVIRUSES

A group of retroviruses that includes HIV. Virus derivatives that are engineered to be replication-defective can be used as expression vectors. Lentiviral vectors have advantages over retroviral vectors because of their ability to infect non-dividing human cells, particularly neurons.

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Figure 1: α-Synuclein conformations.
Figure 2: Mechanisms of α-synuclein and MPTP toxicity.
Figure 3: Relationship between chaperone molecules and α-synuclein toxicity.
Figure 4: Generation of animal models of the synucleinopathies.