γ-Synucleinopathy: Neurodegeneration associated with overexpression of the mouse protein

Human Molecular Genetics

Volumn 18, Issue 10, 2009, Pages 1779-1794

  Ninkina, Natalia ^a   Peters, Owen ^a   Millership, Steven ^a   Salem, Hatem ^a   van der Putten, Herman ^b   Buchman, Vladimir L ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA SYNUCLEIN; THY 1 ANTIGEN;

AGE DISTRIBUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOSIS; CONTROLLED STUDY; DEGENERATIVE DISEASE; GENE FUNCTION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; MOUSE; NERVE CELL NECROSIS; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NONHUMAN; PERIKARYON; PRIORITY JOURNAL; PROTEIN AGGREGATION; SPINAL CORD DISEASE; SPINAL CORD MOTONEURON; TRANSGENIC MOUSE;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; GAMMA-SYNUCLEIN; GENE EXPRESSION; HUMANS; INCLUSION BODIES; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOTOR NEURONS; NERVE DEGENERATION; SPINAL CORD;

ANIMALIA; MUS MUSCULUS;

EID: 65449181204     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp090     Document Type: Article

References (72)

1. Cookson, M.R. and van der Brug, M. (2008) Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp. Neurol., 209, 5-11.
2. Park, J.Y. and Lansbury, P.T. Jr (2003) Beta-synuclein inhibits formation of alpha-synuclein protofibrils: A possible therapeutic strategy against Parkinson's disease. Biochemistry, 42, 3696-3700.
3. da Costa, C.A., Masliah, E. and Checler, F. (2003) Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: Cross-talk with alpha-synuclein and implication for Parkinson's disease. J. Biol. Chem., 278, 37330-37335.
4. Windisch, M., Hutter-Paier, B., Rockenstein, E., Hashimoto, M., Mallory, M. and Masliah, E. (2002) Development of a new treatment for Alzheimer's disease and Parkinson's disease using anti-aggregatory beta-synuclein-derived peptides. J. Mol. Neurosci., 19, 63-69.
5. Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M. and Masliah, E. (2001) β-Synuclein inhibits alpha-synuclein aggregation: A possible role as an anti-parkinsonian factor. Neuron, 32, 213-223.
6. Fan, Y., Limprasert, P., Murray, I.V., Smith, A.C., Lee, V.M., Trojanowski, J.Q., Sopher, B.L. and La Spada, A.R. (2006) Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression. Hum. Mol. Genet., 15, 3002-3011.
7. Hashimoto, M., Rockenstein, E., Mante, M., Crews, L., Bar-On, P., Gage, F.H., Marr, R. and Masliah, E. (2004) An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model. Gene Ther., 11, 1713-1723.
8. Sung, Y.H. and Eliezer, D. (2007) Residual structure, backbone dynamics, and interactions within the synuclein family. J. Mol. Biol., 372, 689-707.
9. Volles, M.J. and Lansbury, P.T. Jr (2003) Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson's disease. Biochemistry, 42, 7871-7878.
10. Dev, K.K., Hofele, K., Barbieri, S., Buchman, V.L. and van der Putten, H. (2003) Part II: Alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharmacology, 45, 14-44.
11. Biere, A.L., Wood, S.J., Wypych, J., Steavenson, S., Jiang, Y., Anafi, D., Jacobsen, F.W., Jarosinski, M.A., Wu, G.M., Louis, J.C. et al. (2000) Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed its homologs. J. Biol. Chem., 275, 34574-34579.
12. Uversky, V.N., Li, J., Souillac, P., Millett, I.S., Doniach, S., Jakes, R., Goedert, M. and Fink, A.L. (2002) Biophysical properties of the synucleins and their propensities to fibrillate: Inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J. Biol. Chem., 277, 11970-11978.
13. Zibaee, S., Jakes, R., Fraser, G., Serpell, L.C., Crowther, R.A. and Goedert, M. (2007) Sequence determinants for amyloid fibrillogenesis of human alpha-synuclein. J. Mol. Biol., 374, 454-464.
14. Saha, A.R., Ninkina, N.N., Hanger, D.P., Anderton, B.H., Davies, A.M. and Buchman, V.L. (2000) Induction of neuronal death by alpha-synuclein. Eur. J. Neurosci., 12, 3073-3077.
15. Buchman, V.L., Adu, J., Pinon, L.G., Ninkina, N.N. and Davies, A.M. (1998) Persyn, a member of the synuclein family, influences neurofilament network integrity. Nat. Neurosci., 1, 101-103.
16. Surgucheva, I., McMahan, B., Ahmed, F., Tomarev, S., Wax, M.B. and Surguchov, A. (2002) Synucleins in glaucoma: Implication of gamma-synuclein in glaucomatous alterations in the optic nerve. J. Neurosci. Res., 68, 97-106.
17. Rockenstein, E., Hansen, L.A., Mallory, M., Trojanowski, J.Q., Galasko, D. and Masliah, E. (2001) Altered expression of the synuclein family mRNA in Lewy body and Alzheimer's disease. Brain Res., 914, 48-56.
18. Mukaetova-Ladinska, E.B., Milne, J., Andras, A., Abdel-All, Z., Cerejeira, J., Greally, E., Robson, J., Jaros, E., Perry, R., McKeith, I.G. et al. (2008) Alpha- and gamma-synuclein proteins are present in cerebrospinal fluid and are increased in aged subjects with neurodegenerative and vascular changes. Dement. Geriatr. Cogn. Disord., 26, 32-42.
19. Mori, F., Hayashi, S., Yamagishi, S., Yoshimoto, M., Yagihashi, S., Takahashi, H. and Wakabayashi, K. (2002) Pick's disease: Alpha- and beta-synuclein-immunoreactive Pick bodies in the dentate gyrus. Acta Neuropathol. (Berl.), 104, 455-461.
20. Galvin, J.E., Giasson, B., Hurtig, H.I., Lee, V.M. and Trojanowski, J.Q. (2000) Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. Am. J. Pathol., 157, 361-368.
21. Galvin, J.E., Uryu, K., Lee, V.M. and Trojanowski, J.Q. (1999) Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. Proc. Natl Acad. Sci. USA, 96, 13450-13455.
22. Mu, X., Beremand, P.D., Zhao, S., Pershad, R., Sun, H., Scarpa, A., Liang, S., Thomas, T.L. and Klein, W.H. (2004) Discrete gene sets depend on POU domain transcription factor Brn3b/Brn-3.2/POU4f2 for their expression in the mouse embryonic retina. Development, 131, 1197-1210.
23. Brenz Verca, M.S., Bahi, A., Boyer, F., Wagner, G.C. and Dreyer, J.L. (2003) Distribution of alpha- and gamma-synucleins in the adult rat brain and their modification by high-dose cocaine treatment. Eur. J. Neurosci., 18, 1923-1938.
24. Soto, I., Oglesby, E., Buckingham, B.P., Son, J.L., Roberson, E.D., Steele, M.R., Inman, D.M., Vetter, M.L., Horner, P.J. and Marsh-Armstrong, N. (2008) Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. J. Neurosci., 28, 548-561.
25. Buckingham, B.P., Inman, D.M., Lambert, W., Oglesby, E., Calkins, D.J., Steele, M.R., Vetter, M.L., Marsh-Armstrong, N. and Horner, P.J. (2008) Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma. J. Neurosci., 28, 2735-2744.
26. Wang, Y.L., Takeda, A., Osaka, H., Hara, Y., Furuta, A., Setsuie, R., Sun, Y.J., Kwon, J., Sato, Y., Sakurai, M. et al. (2004) Accumulation of beta-and gamma-synucleins in the ubiquitin carboxyl-terminal hydrolase L1-deficient gad mouse. Brain Res., 1019, 1-9.
27. van der Putten, H., Wiederhold, K.H., Probst, A., Barbieri, S., Mistl, C., Danner, S., Kauffmann, S., Hofele, K., Spooren, W.P., Ruegg, M.A. et al. (2000) Neuropathology in mice expressing human alpha-synuclein. J. Neurosci., 20, 6021-6029.
28. Rockenstein, E., Mallory, M., Hashimoto, M., Song, D., Shults, C.W., Lang, I. and Masliah, E. (2002) Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J. Neurosci. Res. 68, 568-578.
29. Chandra, S., Gallardo, G., Fernandez-Chacon, R., Schluter, O.M. and Sudhof, T.C. (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell, 123, 383-396.
30. Zhou, W., Schutzman, J. and Freed, C.R. (2008) Transgenic mice overexpressing tyrosine-to-cysteine mutant human alpha-synuclein: A progressive neurodegenerative model of diffuse Lewy body disease. J. Biol. Chem., 283, 9863-9870.
31. Buchman, V.L., Hunter, H.J., Pinon, L.G., Thompson, J., Privalova, E.M., Ninkina, N.N. and Davies, A.M. (1998) Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system. J. Neurosci., 18, 9335-9341.
32. Ninkina, N., Papachroni, K., Robertson, D.C., Schmidt, O., Delaney, L., O'Neill, F., Court, F., Rosenthal, A., Fleetwood-Walker, S.M., Davies, A.M. et al. (2003) Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene. Mol. Cell. Biol., 23, 8233-8245.
33. Yavich, L., Oksman, M., Tanila, H., Kerokoski, P., Hiltunen, M., van Groen, T., Puolivali, J., Mannisto, P.T., Garcia-Horsman, A., MacDonald, E. et al. (2005) Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human alpha-synuclein. Neurobiol. Dis., 20, 303-313.
34. Masliah, E., Rockenstein, E., Veinbergs, I., Mallory, M., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A. and Mucke, L. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: Implications for neurodegenerative disorders. Science, 287, 1265-1269.
35. Lee, M.K., Stirling, W., Xu, Y., Xu, X., Qui, D., Mandir, A.S., Dawson, T.M., Copeland, N.G., Jenkins, N.A. and Price, D.L. (2002) Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 → Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc. Natl Acad. Sci. USA, 99 8968-8973.
36. Gispert, S., Del Turco, D., Garrett, L., Chen, A., Bernard, D.J., Hamm-Clement, J., Korf, H.W., Deller, T., Braak, H., Auburger, G. et al. (2003) Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation. Mol. Cell. Neurosci., 24, 419-429.
37. Giasson, B.I., Duda, J.E., Quinn, S.M., Zhang, B., Trojanowski, J.Q. and Lee, V.M. (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron, 34, 521-533.
38. Freichel, C., Neumann, M., Ballard, T., Muller, V., Woolley, M., Ozmen, L., Borroni, E., Kretzschmar, H.A., Haass, C., Spooren, W. et al. (2007) Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice. Neurobiol. Aging, 28, 1421-1435.
39. Fleming, S.M., Salcedo, J., Fernagut, P.O., Rockenstein, E., Masliah, E., Levine, M.S. and Chesselet, M.F. (2004) Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J. Neurosci., 24, 9434-9440.
40. Sharp, P.S., Akbar, M.T., Bouri, S., Senda, A., Joshi, K., Chen, H.J., Latchman, D.S., Wells, D.J. and de Belleroche, J. (2008) Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression. Neurobiol. Dis., 30, 42-55.
41. Maatkamp, A., Vlug, A., Haasdijk, E., Troost, D., French, P.J. and Jaarsma, D. (2004) Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS-SOD1 mice. Eur. J. Neurosci., 20, 14-28.
42. Bruening, W., Roy, J., Giasson, B., Figlewicz, D.A., Mushynski, W.E. and Durham, H.D. (1999) Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J. Neurochem., 72, 693-699.
43. Adachi, H., Waza, M., Tokui, K., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M. and Sobue, G. (2007) CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model. J. Neurosci., 27, 5115-5126.
44. Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Pagoulatos, G., Angelidis, C., Kusakabe, M., Yoshiki, A., Kobayashi, Y., Doyu, M. et al. (2003) Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J. Neurosci., 23, 2203-2211.
45. Zhai, J., Lin, H., Julien, J.P. and Schlaepfer, W.W. (2007) Disruption of neurofilament network with aggregation of light neurofilament protein: A common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1. Hum. Mol. Genet., 16, 3103-3116.
46. Evgrafov, O.V., Mersiyanova, I., Irobi, J., Van Den Bosch, L., Dierick, I., Leung, C.L., Schagina, O., Verpoorten, N., Van Impe, K., Fedotov, V. et al. (2004) Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat. Genet., 36, 602-606.
47. Ackerley, S., James, P.A., Kalli, A., French, S., Davies, K.E. and Talbot, K. (2006) A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes. Hum. Mol. Genet., 15, 347-354.
48. Springer, W. and Kahle, P.J. (2006) Mechanisms and models of alpha-synuclein-related neurodegeneration. Curr. Neurol. Neurosci. Rep., 6, 432-436.
49. Chesselet, M.F. (2008) In vivo alpha-synuclein overexpression in rodents: A useful model of Parkinson's disease? Exp. Neurol., 209, 22-27.
50. Buchman, V.L. and Ninkina, N. (2008) Modulation of alpha-synuclein expression in transgenic animals for modelling synucleinopathies - is the juice worth the squeeze? Neurotox. Res., 14, 329-341.
51. Yazawa, I., Giasson, B.I., Sasaki, R., Zhang, B., Joyce, S., Uryu, K., Trojanowski, J.Q. and Lee, V.M. (2005) Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron, 45, 847-859.
52. Masliah, E., Rockenstein, E., Veinbergs, I., Sagara, Y., Mallory, M., Hashimoto, M. and Mucke, L. (2001) Beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc. Natl Acad. Sci. USA, 98, 12245-12250.
53. Klucken, J., Shin, Y., Masliah, E., Hyman, B.T. and McLean, P.J. (2004) Hsp70 reduces alpha-synuclein aggregation and toxicity. J. Biol. Chem., 279, 25497-25502.
54. Kahle, P.J., Neumann, M., Ozmen, L., Muller, V., Odoy, S., Okamoto, N., Jacobsen, H., Iwatsubo, T., Trojanowski, J.Q., Takahashi, H. et al. (2001) Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am. J. Pathol. 159, 2215-2225.
55. Gomez-Isla, T., Irizarry, M.C., Mariash, A., Cheung, B., Soto, O., Schrump, S., Sondel, J., Kotilinek, L., Day, J., Schwarzschild, M.A. et al. (2003) Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice. Neurobiol. Aging, 24, 245-258.
56. Sampathu, D.M., Giasson, B.I., Pawlyk, A.C., Trojanowski, J.Q. and Lee, V.M. (2003) Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies. Am. J. Pathol., 163, 91-100.
57. Neumann, M., Kahle, P.J., Giasson, B.I., Ozmen, L., Borroni, E., Spooren, W., Muller, V., Odoy, S., Fujiwara, H., Hasegawa, M. et al. (2002) Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J. Clin. Invest., 110, 1429-1439.
58. Xiao, S., McLean, J. and Robertson, J. (2006) Neuronal intermediate filaments and ALS: A new look at an old question. Biochim. Biophys. Acta, 1762, 1001-1012.
59. Lariviere, R.C. and Julien, J.P. (2004) Functions of intermediate filaments in neuronal development and disease. J. Neurobiol., 58, 131-148.
60. Julien, J.P. and Kriz, J. (2006) Transgenic mouse models of amyotrophic lateral sclerosis. Biochim. Biophys. Acta, 1762, 1013-1024.
61. Bruijn, L.I., Miller, T.M. and Cleveland, D.W. (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci., 27, 723-749.
62. Perez-Olle, R., Leung, C.L. and Liem, R.K. (2002) Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation. J. Cell Sci., 115, 4937-4946.
63. Perez-Olle, R., Jones, S.T. and Liem, R.K. (2004) Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models. Hum. Mol. Genet., 13, 2207-2220.
64. Mersiyanova, I.V., Perepelov, A.V., Polyakov, A.V., Sitnikov, V.F., Dadali, E.L., Oparin, R.B., Petrin, A.N. and Evgrafov, O.V. (2000) A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am. J. Hum. Genet., 67, 37-46.
65. De Jonghe, P., Mersivanova, I., Nelis, E., Del Favero, J., Martin, J.J., Van Broeckhoven, C., Evgrafov, O. and Timmerman, V. (2001) Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann. Neurol., 49, 245-249.
66. Beaulieu, J.M., Jacomy, H. and Julien, J.P. (2000) Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J. Neurosci., 20, 5321-5328.
67. McLean, J.R., Sanelli, T.R., Leystra-Lantz, C., He, B.P. and Strong, M.J. (2005) Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(-/-) mice. Glia 52, 59-69.
68. Robertson, D.C., Schmidt, O., Ninkina, N., Jones, P.A., Sharkey, J. and Buchman, V.L. (2004) Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. J. Neurochem., 89, 1126-1136.
69. Carter, R.J., Lione, L.A., Humby, T., Mangiarini, L., Mahal, A., Bates, G.P., Dunnett, S.B. and Morton, A.J. (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci., 19, 3248-3257.
70. Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 25, 402-408.
71. Spillantini, M.G., Crowther, R.A., Jakes, R., Hasegawa, M. and Goedert, M. (1998) Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc. Natl Acad. Sci. USA, 95, 6469-6473.
72. Serpell, L.C., Berriman, J., Jakes, R., Goedert, M. and Crowther, R.A. (2000) Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc. Natl Acad. Sci. USA, 97, 4897-4902.