Transgenic mouse models of Parkinson's disease and Huntington's disease

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 4, 2010, Pages 455-470

  Skaper, Stephen D ^a   Giusti, Pietro ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Cag repeat; Dopaminergic; Huntington's disease; Mouse; Neurodegeneration; Parkinson's disease; Polyglutamine disease; Striatum; Transgenic

Indexed keywords

CALMODULIN INHIBITOR; DJ 1 PROTEIN; HUNTINGTIN; HUNTINGTIN INTRABODY; INTRABODY C4; INTRABODY EM48; INTRABODY HAPP1; INTRABODY MW7; LEUCINE RICH REPEAT KINASE 2; PARKIN; POLYGLUTAMINE; RECOMBINANT ANTIBODY; UNCLASSIFIED DRUG;

ARTICLE; CLINICAL FEATURE; DISEASE COURSE; DISEASE MODEL; HEREDITY; HUMAN; HUNTINGTON CHOREA; MOUSE; NONHUMAN; NUCLEOTIDE REPEAT; PARKINSON DISEASE; PATHOGENESIS; PATHOPHYSIOLOGY; TRANSGENIC MOUSE; ANIMAL; GENE; GENE TARGETING; GENETICS; MUTATION; PHYSIOLOGY;

ANIMALS; DISEASE MODELS, ANIMAL; GENE KNOCK-IN TECHNIQUES; GENES; HUMANS; HUNTINGTON DISEASE; MICE; MICE, TRANSGENIC; MUTATION; PARKINSON DISEASE;

EID: 77954335273     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710791556186     Document Type: Article

References (233)

1. Forno, L.S. Neuropathology of Parkinson's disease. J. Neuropathol. Exp. Neurol., 1996, 55, 259-272.
2. Gelb, D.J.; Oliver, E.; Gilman, S. Diagnostic criteria for Parkinson disease. Arch. Neurol., 1999, 56, 33-39.
3. Braak, H.; Del Tredici, K.; Rüb, U.; de Vos, R.A.; Jansen Steur, E.N.; Braak, E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging, 2003, 24, 197-211.
4. Dauer, W.; Przedborski, S. Parkinson's disease: mechanisms and models. Neuron, 2003, 39, 889-909.
5. Dorsey, E.R.; Constaninescu, R.; Thompson, J.P.; Biglan, K.M.; Holloway, R.G.; Kieburtz, K.; Marshall, F.J.; Ravina, B.M.; Schifitto, G.; Siderowf, A.; Tanner, C.M. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology, 2007, 68, 384-386.
6. Cookson, M.R. The biochemistry of Parkinson's disease. Annu. Rev. Biochem., 2005, 74, 29-52.
7. Schulz, J.B.; Falkenburger, B.H. Neuronal pathology in Parkinson's disease. Cell Tissue Res., 2004, 318, 135-147.
8. Polymeropoulos, M.H.; Lavedan, C.; Leroy, E.; Ide, S.E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.; Stenroos, E.S.; Chandrasekharappa, S.; Athanassiadou, A.; Papapetropoulos, T.; Johnson, W.G.; Lazzarini, A.M.; Duvoisin, R.C.; Di Iorio, G.; Golbe, L.I.; Nussbaum, R.L. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science, 1997, 276, 2045-2047.
9. Kitada, T.; Asakawa, S.; Hattori, N.; Matsumine, H.; Yamamura, Y.; Minoshima, S.; Yokochi, M.; Mizuno, Y.; Shimizu, N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 1998, 392, 606-608.
10. Bonifati, V.; Rizzu, P.; van Baren, M.J.; Schaap, O.; Breedveld, G.J.; Krieger, E.; Dekker, M.C.J.; Squitieri, F.; Ibanez, P.; Joosse, M.; van Dongen, J.W.; Vanacore, N.; van Swieten, J.C.; Brice, A.; Meco, G.; van Dujin, C.M.; Oostra, B.A.; Heutink, P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science, 2003, 299, 256-259.
11. Singleton, A.B.; Farrer, M.; Johnson, J.; Singleton, A.; Hague, S.; Kachergus, J.; Hulihan, M.; Peuralinna, T.; Dutra, A.; Nussbaum, R.; Lincoln, S.; Crawley, A.; Hanson, M.; Maraganore, D.; Adler, C.; Cookson, M.R.; Muenter, M.; Baptista, M.; Miller, D.; Blancato, J.; Hardy, J.; Gwinn-Hardy, K. α-Synuclein locus triplication causes Parkinson's disease. Science, 2003, 302, 841.
12. Chartier-Harlin, M.C.; Kachergus, J.; Roumier, C.; Mouroux, V.; Douay, X.; Lincoln, S.; Levecque, C.; Larvor, L.; Andrieux, J.; Hulihan, M.; Waucquier, N.; Defebvre, L.; Amouyel, P.; Farrer, M.; Destée, A. α-Synuclein locus duplication as a cause of familial Parkinson's disease. Lancet, 2004, 364, 1167-1169.
13. Paisán-Ruiz, C.; Jain, S.; Evans, E.W.; Gilks, W.P.; Simón, J.; van der Brug, M.; López de Munain, A.; Aparicio, S.; Gil, A.M.; Khan, N.; Johnson, J.; Martinez, J.R.; Nicholl, D.; Carrera, I.M.; Peňa, A.S.; de Silva, R.; Lees, A.; Marti-Massó, J.F.; Pérez-Tur, J.; Wood, N.W.; Singleton, A.B. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron, 2004, 44, 595-600.
14. Valente, E.M.; Abou-Sleiman, P.M.; Caputo, V.; Muqit, M.M.K.; Harvey, K.; Gispert, S.; Ali, Z.; Del Turco, D.; Bentivoglio, A.R.; Healy, D.G.; Albanese, A.; Nussbaum, R.; González-Maldonado, R.; Deller, T.; Salvi, S.; Cortelli, P.; Gilks, W.P.; Latchman; D.S.; Harvey, R.J.; Dallapiccola, B.; Auburger, G.; Wood, N.W. Hereditary early-onset parkinson's disease caused by mutations in PINK1. Science, 2004, 304, 1158-1160.
15. Zimprich, A.; Biskup, S.; Leitner, P.; Lichtner, P.; Farrer, M.; Lincoln, S.; Kachergus, J.; Hulihan, M.; Uitti, R.J.; Calne, D.B.; Stoessl, A.J.; Pfeiffer, R.F.; Patenge, N.; Carbajal, I.C.; Vieregge, P.; Asmus, F.; Müller-Myhsok, B.; Dickson, D.W.; Meitinger, T.; Strom, T.M.; Wszolek, Z.K.; Gasser, T. Mutations in LRRK2 cause autosomal dominant parkinsonism with pleomorphic pathology. Neuron, 2004, 44, 601-607.
16. Leroy, E.; Boyer, R.; Auburger, G.; Leube, B.; Ulm, G.; Mezey, E.; Harta, G.; Brownstein, M.J.; Jonnalagada, S.; Chernova, T.; Dehejia, A.; Lavedan, C.; Gasser, T.; Steinbach, PJ.; Wilkinson, K.D.; Polymeropoulos, M.H. The ubiquitin pathway in Parkinson's disease. Nature, 1998, 395, 451-452.
17. Hardy, J.; Cookson, M.R.; Singleton, A. Genes and parkinsonism. Lancet Neurol., 2003, 2, 221-228.
18. Greenamyre, J.T.; Hastings, T.G. Parkinson's - divergent causes, convergent mechanisms. Science, 2004, 304, 1120-1122.
19. Hedrich, K., Djarmati, A.; Schäfer, N.; Hering, R.; Wellenbrock, C.; Weiss, P.H.; Hilker, R.; Vieregge, P.; Ozelius, L.J.; Heutink, P.; Bonifati, V.; Schwinger, E.; Lang, AE.; Noth, J.; Bressman, SB.; Pramstaller, P.P.; Riess, O.; Klein, C. DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology, 2004, 62, 389-394.
20. Zhang, L.; Shimoji, M.; Thomas, B.; Moore, D.J.; Yu, S.-W.; Marupudi, N.I.; Torp, R.; Torgner, I.A.; Ottersen, O.P.; Dawson, TM.; Dawson, V.L. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum. Mol. Genet., 2005, 14, 2063-2073.
21. Taira, T.; Saito, Y.; Niki, T.; Iguchi-Ariga, S.M.; Takahashi, K.; Ariga, H. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep., 2004, 5, 213-218.
22. Patera, J.-C.; Leng, A.; Weber, E.; Feldon, J.; Büeler, H. DJ-1 and Parkin modulate dopamine-dependent behaviour and inhibit MPTP-induced nigral dopamine neuron loss in mice. Mol. Ther., 2007, 15, 698-704.
23. Inden, M.; Taira, T.; Kitamura, Y.; Yanagida, T.; Tsuchiya, D.; Takata, K.; Yanagisawa, D.; Nishimura, K.; Taniguchi, T.; Kiso, Y.; Yoshimoto, K.; Agatsuma, T.; Koide-Yoshida, S.; Iguchi-Ariga, S.M.M.; Shimohama, S.; Ariga, H. PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. Neurobiol. Dis., 2006, 24, 144-158.
24. Zhou, W.; Freed, C.R. DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibita A53T -synuclein toxicity. J. Biol. Chem., 2005, 280, 43150-43158.
25. Zhou, W.; Zhu, M.; Wilson, M.A.; Petsko, G.A.; Fink, A.L. The oxidation state of DJ-1 regulates its chaperone activity toward α-synuclein. J. Mol. Biol., 2006, 356, 1036-1048.
26. Goldberg, M.S.; Pisani, A.; Haburcak, M.; Vortherms, T.A.; Kitada, T.; Costa, C.; Tong, Y.; Martella, G.; Tscherter, A.; Martins, A.; Bernardi, G.; Roth, B.L.; Pothos, E.N.; Calabresi, P.; Shen, J. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron, 2005, 45, 489-496.
27. Chen, L.; Cagniard, B.; Mathews, T.; Jones, S.; Koh, H.C.; Ding, Y.; Carvey, P.M.; Ling, Z.; Kang, U.J.; Zhuang, X. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem., 2005, 280, 21418-21426.
28. Kim, R.H.; Smith, P.D.; Aleyasin, H.; Hayley, S.; Mount, M.P.; Pownall, S.; Wakeham, A.; You-Ten, A.J.; Kalia, S.K.; Horne, P.; Westaway, D.; Lozano, A.M.; Anisman, H.; Park, D.S.; Mak, T.W. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress, Proc. Natl. Acad. Sci. USA, 2005, 102, 5215-5220.
29. Bretaud, S.; Allen, C.; Ingham, P.W.; Bandmann, O. p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease. J. Neurochem., 2007, 100, 1626-1635.
30. + ATPase. Neurobiol. Dis., 2006, 23, 54-60.
31. Yang, Y.; Gehrke, S.; Haque, M.E.; Imai, Y.; Imai, Y.; Kosek, J.; Yang, L.; Beal, M.F.; Nishimura, I.; Wakamatsu, K.; Ito, S.; Takahashi, R.; Lu, B. Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signalling. Proc. Natl. Acad. Sci. USA, 2005, 102, 13670-13675.
32. Junn, E.; Taniguchi, H.; Jeong, B.S.; Zhao, X.; Ichijo, H.; Mouradian, M.M. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc. Natl. Acad. Sci. USA, 2005, 102, 9691-9696.
33. Zhong, N.; Kim, C.Y.; Rizzu, P.; Geula, C.; Porter, D.R.; Pothos, E.N.; Squitieri, F.; Heutink, P.; Xu, J. DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor. J. Biol. Chem., 2006, 281, 20940-20948.
34. Schapira, A.H. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol. 2008, 7, 97-109.
35. Hayashi, S.; Wakabayashi, K.; Ishikawa, A.; Nagai, H.; Saito, M.; Maruyama, M.; Takahashi, T.; Ozawa, T.; Tsuji, S.; Takahashi, H. An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene. Mov. Disord., 2000, 15, 884-888.
36. Pramstaller, P.P.; Schlossmacher, M.G.; Jacques, T.S.; Scaravilli, F.; Eskelson, C.; Pepivani, I.; Hedrich, K.; Adel, S.; Gonzales-McNeal, M.; Hilker, R.; Kramer, P.L.; Klein, C. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann. Neurol., 2005, 58, 411-422.
37. Shimura, H.; Hattori, N.; Kubo, S.; Mizuno, Y.; Asakawa, S.; Minoshima, S.; Shimizu, N.; Iwai, K.; Chiba, T.; Tanaka, K.; Suzuki, T. Familial parkinson disease gene product, Parkin, is a ubiquitin-protein ligase. Nat. Genet., 2000, 3, 302-305.
38. Darios, F.; Corti, O.; Lücking, C.B.; Hampe, C.; Muriel, M.-P.; Abbas, N.; Gu, W.-J.; Hirsch, E.C.; Rooney, T.; Ruberg, M.; Brice, A. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum. Mol. Genet., 2003, 12, 517-526.
39. Kuroda, Y.; Mitsui, T.; Kunishige, M.; Shono, M.; Akaike, M.; Azuma, H.; Matsumoto, T. Parkin enhances mitochondrial biogenesis in proliferating cells. Hum. Mol. Genet., 2006, 15, 883-895.
40. Wood-Kaczmar, A.; Gandhi, S.; Wood, N.W. Understanding the molecular causes of Parkinson's disease. Trends Mol. Med., 2006, 12, 521-528.
41. Petrucelli L.; O'Farrell, C.; Lockhart, P.J.; Baptista, M.; Kehoe, K.; Vink, L.; Choi, P.; Wolozin, B.; Farrer, M.; Hardy, J.; Cookson, M.R. Parkin protects against the toxicity associated with mutant α-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron, 2002, 36, 1007-1019.
42. Staropoli, J.F.; McDermott, C.; Martinat, C.; Schulman, B.; Demireva, E.; Abeliovich, A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron, 2003, 37, 735-749.
43. Palacino, J.J.; Sagi, D.; Goldberg, M.S.; Krauss, S.; Motz, C.; Wacker, M.; Klose, J.; Shen, J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J. Biol. Chem., 2004, 279, 18614-18622.
44. Henn, I.H.; Bouman, L.; JSchlehe, J.S.; Schlierf, A.; Schramm, J.E.; Wegener, E.; Nakaso, K.; Culmsee, C.; Berninger, B.; Krappmann, D.; Tatzelt, J.; Winklhofer, K.F. Parkin mediates neuroprotection through activation of I B kinase/nuclear factor-kB signalling. J. Neurosci., 2007, 27, 1868-1878.
45. Goldberg, M.S.; Fleming, S.M.; Palacino, J.J.; Cepeda, C.; Lam, H.A.; Bhatnagar, A.; Meloni, E.G.; Wu, N.; Ackerson, L.C.; Klapstein, G.J.; Gajendiran, M.; Roth, B.L.; Chesselet, M.-F.; Maidment, N.T.; Levine, M.S.; Shen J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem., 2003, 278, 43628-43635.
46. Itier, J.-M.; Ibáñez, P.; Mena, M.A.; Abbas, N.; Cohen-Salmon, C.; Bohme, G.A.; Laville, M.; Pratt, J.; Corti, O.; Pradier, L.; Ret, G.; Joubert, C.; Periquet, M.; Araujo, F.; Negroni, J.; Casarejos, M.J.; Canals, S.; Solano, R.; Serrano, A.; Gallego, E.; M Sánchez, M.; Denèfle, P.; Benavides, J.; Tremp, G.; Rooney, T.A.; Brice, A.; Garcia de Yébenes, J. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum. Mol. Genet., 2003, 12, 2277-2291.
47. Perez, F.A.; Palmiter, R.D. Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. USA, 2005, 102, 2174-2179.
48. von Coelln R.; Thomas, B.; Savitt, J.M.; Lim, K.L.; Sasaki, M.; Hess, E.J.; Dawson, V.L.; Dawson, T.M. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc. Natl. Acad. Sci. USA, 2004, 101, 10744-10749.
49. Thomas, B.; von Coelln, R.; Mandir, A.S.; Trinkaus, D.B.; Farah, M.H.; Leong Lim, K.; Calingasan, N.Y.; Beal, M.F.; Dawson, V.L.; Dawson, T.M. MPTP and DSP-4 susceptibility of substantia nigra and locus coeruleus catecholaminergic neurons in mice is independent of parkin activity. Neurobiol. Dis., 2007, 26, 312-322.
50. Perez, F.A.; Curtis, W.R.; Palmiter, R.D. Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity. BMC Neurosci., 2005, 6, 71.
51. Stichel, C.C.; Zhu, X.-R.; Bader, V.; Linnartz, B.; Schmidt, S.; Lübbert, H. Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage. Hum. Mol. Genet., 2007, 16, 2377-2393.
52. von Coelln, R.; Thomas, B.; Andrabi, S.A.; Lim, K.L.; Savitt, J.M.; Saffary, R.; Stirling, W.; Bruno, K.; Hess, E.J.; Lee, M.K.; Dawson, V.L.; Dawson, T.M. Inclusion body formation and neurodegeneration are parkin independent in a mouse model of α-synucleinopathy. J. Neurosci., 2006, 26, 3685-3696.
53. Solano, R.M.; Menéndez, J.; Casarejos, M.J.; Rodríguez-Navarro, J.A.; Garcia de Yébenes, J.; Mena, M.A. Midbrain neuronal cultures from parkin mutant mice are resistant to nitric oxide-induced toxicity. Neuropharmacology, 2006, 51, 327-340.
54. Greene, J.C.; Whitworth, A.J.; Kuo, I.; Andrews, L.A.; Feany, M.B.; Pallanck, L.J. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl. Acad. Sci. USA, 2003, 100, 4078-4083.
55. Sang, T.-K.; Chang, H.-Y.; Lawless, G.M.; Ratnaparkhi, A.; Mee, L.; Ackerson, L.C.; Maidment, N.T.; Krantz, D.E.; Jackson, G.R. A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine. J. Neurosci., 2007, 27, 981-992.
56. Valente, E.M.; Salvi, S.; Ialongo, T.; Marongiu, R.; Elia, E.A.; Caputo, V.; Romito, L.; Albanese, A.; Dallapiccola, B.; Bentivoglio, A.R. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann. Neurol., 2004, 56, 336-341.
57. Silvestri, L.; Caputo, V.; Bellacchio, E.; Atorino, L.; Dallapiccola, B.; Valente, E.M.; Casari, G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum. Mol. Genet., 2005, 14, 3477-3492.
58. Leutenegger, A.-L.; Salih, M.A.M.; Ibáñez, P.; Mukhtar, M.M.; Lesage, S.; Arabi, A.; Lohmann, E.; Dürr, A.; Ahmed, A.E.M.; Brice, A. Juvenile onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation of PINK1. Arch. Neurol., 2006, 63, 1257-1261.
59. Beilina, A.; Van Der Brug, M.; Ahmad, R.; Kesavapany, S.; Miller, D.W.; Petsko, G.A.; Cookson, M.R. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc. Natl. Acad. Sci. USA, 2005, 102, 5703-5708.
60. Sim, C.H.; Lio, D.S.; Mok, S.S.; Masters, C.L.; Hill, A.F.; Culvenor, J.G.; Cheng, H.C. C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum. Mol. Genet., 2006, 15, 3251-3262.
61. Scheele, C.; Petrovic, N.; Faghihi, M.A.; Lassmann, T.; Fredriksson, K.; Rooyackers, O.; Wahlestedt, C.; Good, L.; Timmons, J.A. The human PINK1 locus is regulated in vivo by non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genom., 2007, 8, 74.
62. Kitada, T.; Pisani, A.; Porter, D.R.; Yamaguchi, H.; Tscherter, A.; Martella, G.; Bonsi, P.; Zhang, C.; Pothos, E.N.; Shen, J. Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc. Natl. Acad. Sci. USA, 2007, 104, 11441-11446.
63. Gandhi, S.; Wood-Kaczmar, A.; Yao, Z.; Plun-Favreau, H.; Deas, E.; Klupsch, K.; Downward, J.; Latchman, D.S.; Tabrizi, S.J.; Wood, N.W.; Duchen, M.R.; Abramov, A.Y. PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol. Cell, 2009, 33, 627-638.
64. Gispert, S.; Ricciardi, F.; Kurz, A.; Azizov, M.; Hoepken, H.-H.; Becker, D.; Voos, W.; Leuner, K.; Müller, W.E.; Kudin, A.P.; Kunz, W.S.; Zimmermann, A.; Roeper, J.; Wenzel, D.; Jendrach, M.; García-Arencíbia, M.; Fernández-Ruiz, J.; Huber, L.; Rohrer, H.; Barrera, M.; Reichert, A.S.; Rüb, U.; Chen, A.; Nussbaum, R.L.; Auburger G. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One, 2009, 4, e5777.
65. Clark, I.E., Dodson, M.W.; Jiang, C.; Cao, J.H.; Huh, J.R.; Seol, J.H.; Yoo, S.J.; Hay, B.A.; Guo, M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature, 2006, 441, 1162-1166.
66. Park, J.; Lee, S.B.; Lee, S.; Kim, Y.; Song, S.; Kim, S.; Bae, E.; Kim, J.; Shong, M.; Kim, J.-M.; Chung, J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature, 2006, 441, 1157-1161.
67. Hoepken, H.-H.; Gispert, S.; Morales, B.; Wingerter, O.; Del Turco, D.; Mülsch, A.; Nussbaum, R.L.; Müller, K.; Dröse, S.; Brandt, U.; Deller, T.; Wirth, B.; Kudin, A.P.; Kunz, W.S.; Auburger, G. Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol. Dis., 2007, 25, 401-411.
68. Yang, Y.; Gehrke, S.; Imai, Y.; Huang, Z.; Ouyang, Y.; Wang, J.-W.; Yang, L.; Beal, M.F.; Vogel, H.; Lu, B. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by parkin. Proc. Natl. Acad. Sci. USA, 2006, 103, 10793-10798.
69. Exner, N.; Treske, B.; Paquet, D.; Holmström, K.; Schiesling, C.; Gispert, S.; Carballo-Carbajal, I.; Berg, D.; Hoepken, H.-H.; Gasser, T.; Krüger, R.; Winklhofer, K.F.; Vogel, F.; Reichert, A.S.; Auburger, G.; Kahle, P.J.; Schmid, B.; Haass, C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci., 2007, 27, 12413-12418.
70. Xiong, H.; Wang, D.; Chen, L.; Choo, Y.S.; Ma, H.; Tang, C.; Xia, K.; Jiang, W.; Ronai, Z.; Zhuang, X.; Zhang, Z. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J. Clin. Invest., 2009, 119, 650-660.
71. Farrer, M.; Stone, J.; Mata, I.F.; Lincoln, S.; Kachergus, J.; Hulihan, M.; Strain, K.J.; Maraganore, D.M. LRRK2 mutations in Parkinson disease. Neurology, 2005, 65, 738-740.
72. Mata, I.F.; Kachergus, J.M.; Taylor, J.P.; Lincoln, S.; Aasly, J.; Lynch, T.; Hulihan, M.M.; Cobb, S.A.; Wu, R.-M.; Lu, C.-S.; Lahoz, C.; Wszolek, Z.K.; Farrer, M.J. Lrrk2 pathogenic substitutions in Parkinson's disease. Neurogenetics, 2005, 6, 171-177.
73. Lesage, S.; Dürr, A.; Tazir, M.; Lohmann, E.; Leutennegger, A.L.; Janin, S.; Pollak, P.; Brice, A. French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N. Engl. J. Med., 2006, 354, 422-423.
74. Ozelius, L.J., Senthil, G.; Saunders-Pullman, R.; Ohmann, E.; Deligtisch, A.; Tagliati, M.; Hunt, A.L.; Klein, C.; Henick, B.; Hailpern, S.M.; Lipton, R.B.; Soto-Valencia, J.; Risch, N.; Bressman, S.B. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N. Engl. J. Med., 2006, 354, 424-425.
75. Brice, A. Genetics of Parkinson's disease: LRRK2 on the rise. Brain, 2005, 128, 2760-2762.
76. Berg, D.; Schweitzer, K.J.; Leitner, P.; Zimprich, A.; Lichtner, P.; Belcredi, P.; Brüssel, T.; Schulte, C.; Maass, S.; Nägele, T.; Wszolek, Z.K.; Gasser, T. Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease. Brain, 2005, 128, 3000-3011.
77. Taylor, J.P.; Mata, I.F.; Farrer, M.J. LRRK2: a common pathway for parkinsonism, pathogenesis and prevention? Trends Mol. Med., 2006, 12, 76-82.
78. Bosgraaf, L.; Van Haastert, P.J. Roc, a Ras/GTPase domain in complex proteins. Biochim. Biophys. Acta, 2003, 1643, 5-10.
79. Marin, I. The Parkinson disease gene LRRK2: evolutionary and structural insights. Mol. Biol. Evol., 2006, 23, 2423-2433.
80. Guo, L.; Wang, W.; Chen, S.G. Leucine-rich repeat kinase 2: relevance to Parkinson's disease. Int. J. Biochem. Cell Biol., 2006, 38, 1469-1475.
81. Korr, D.; Toschi, L.; Donner, P.; Pohlenz, H.D.; Kreft, B.; Weiss, B. LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain. Cell Signal., 2005, 18, 910-920.
82. Tagawa, H.; Karnan, S.; Kasugai, Y.; Tuzuki, S.; Suzuki, R.; Hosokawa, Y., Seto, M. MASL1, a candidate oncogene found in amplification at 8p23.1, is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8. Oncogene, 2004, 23, 2576-2581.
83. Schneider-Stock, R.; Roessner, A.; Ullrich, O. DAP-kinase-protector or enemy in apoptotic cell death. Int. J. Biochem. Cell Biol., 2005, 37, 1763-1767.
84. Biskup, S.; Moore, D.J.; Celsi, F.; Higashi, S.; West, A.B.; Andrabi, S.A.; Kurkinen, K.; Yu, S.-W.; Savitt, J.M.; Waldvogel, H.J.; Faull, R.L.; Emson, P.C.; Torp, R.; Ottersen, O.P.; Dawson, T.M.; Dawson, V.L. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann. Neurol., 2006, 60, 557-569.
85. West, A.B.; Moore, D.J.; Biskup, S.; Bugayenko, A.; Smith, W.W.; Ross, C.A.; Dawson, V.L.; Dawson, T.M. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl. Acad. Sci. USA, 2005, 102, 16842-16847.
86. Galter, D.; Westerlund, M.; Carmine, A.; Lindqvist, E.; Sydow, O.; Olson, L. LRRK2 expression linked to dopamine-innervated areas. Ann. Neurol., 2006, 59, 714-719.
87. Taymans, J.-M.; Van den Haute, C.; Baekelandt, V. Distribution of PINK1 and LRRK2 in rat and mouse brain. J. Neurochem., 2006, 98, 951-961.
88. Goldwurm, S.; Di Fonzo, A.; Simons, E.J.; Rohé, C.F.; Zini, M.; Canesi, M.; Tesei, S.; Zecchinelli, A.; Antonini, A.; Mariani, C.; Meucci, N.; Sacilotto, G.; Sironi, F.; Salani, G.; Ferreira, J.; Chien, H.F.; Fabrizio, E.; Vanacore, N.; Dalla Libera, A.; Stocchi, F.; Diroma, C.; Lamberti, P.; Sampaio, C.; Meco, G.; Barbosa, E.; Bertoli-Avella, A.M.; Breedveld, G.J.; Oostra, B.A.; Pezzoli, G.; Bonifati, V. The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor. J.Med. Genet., 2005, 42, e65.
89. Bonifati, V. LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson disease. Neurochem. Res., 2007, 32, 1700-1708.
90. Guo, L., Gandhi, P.N.; Wang, W.; Petersen, R.B.; Wilson-Delfosse, A.L.; Chen, S.G. The Parkinson's disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulated kinase activity. Exp. Cell Res., 2007, 313, 3658-3670.
91. Lewis, P.A.; Greggio, E.; Beilina, A.; Jain, S.; Baker, A.; Cookson, M.R. The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem. Biophys. Res.Comm., 2007, 357, 668-671.
92. Li, X.; Tan, Y.-C.; Poulose, S.; Olanow, C.W.; Huang, X.-Y.; Yue, Z. Leucine-rich repeat kinase 2 (LRRK2/PARK8) possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. J. Neurochem., 2007, 103, 238-247.
93. Greggio, E., Jain, S.; Kingsbury, A.; Bandopadhyay, R.; Lewis, P.; Kaganovich, A.; van der Brug, M.P.; Beilina, A.; Blackinton, J.; Thomas, K.J.; Ahmad, R.; Miller, D.W.; Kesavapany, S.; Singleton, A.; Lees, A.; Harvey, R.J.; Harvey, K.; Cookson, M.R. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis., 2006, 23, 329-341.
94. Smith, W.W.; Pei, Z.; Jiang, H.; Dawson, V.L.; Dawson, T.M.; Ross, C.A. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci., 2006, 9, 1231-1233.
95. West, A.B.; Moore, D.J.; Choi, C.; Andrabi, S.A.; Li, X.; Dikeman, D.; Biskup, S.; Zhang, Z.; Lim, K.-L.; Dawson, V.L.; Dawson, T.M. Parkinson's disease-associated mutations in LRRK2 link enhanced GTPase-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet., 2007, 16, 223-232.
96. Gloeckner, C.J.; Kinkl, N.; Schumacher, A.; Braun, R.J.; O'Neill, E.; Meitinger, T.; Kolch, W.; Prokisch, H.; Ueffing, M. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet., 2006, 15, 223-232.
97. MacLeod, D.; Dowman, J.; Hammond, R.; Leete, T.; Inoue, K.; Abeliovich, A. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron, 2006, 52, 587-593.
98. Plowey, E.D.; Cherra, S.I. 3rd; Liu, Y.-J.; Chu, C.T. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J. Neurochem., 2008, 105, 1048-1056.
99. Jaleel, M.; Nichols, R.J.; Deak, M.; Campbell, D.G.; Gillardon, F.; Knebel, A.; Alessi, D.R. LRRK2 phosphorylates moesin at threonine-588: characterization of how Parkinson's disease mutants affect kinase activity. Biochem. J., 2007, 405, 307-317.
100. Smith, W.W.; Pei, Z.; Jiang, H.; Moore, D.J.; Liang, Y.; West, A.B.; Dawson, V.L.; Dawson, T.M.; Ross C.A. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc. Natl. Acad. Sci. USA, 2005, 102, 18676-18681.
101. Iaccarino, C.; Crosio, C.; Vitale, C.; Sanna, G.; Carri, M.T.; Barone, P. Apoptotic mechanisms in mutant LRRK2-mediated cell death. Hum. Mol. Genet., 2007, 16, 1319-1326.
102. R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat. Neurosci., 2009, 12, 826-828.
103. Lee, S.B.; Kim, W.; Lee, S.; Chung, J. Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem. Biophys. Res. Comm., 2007, 358, 534-539.
104. Wang, D.; Tang, B.; Zhao, G.; Pan, Q.; Xia, K.; Bodmer, R.; Zhang, Z. Dispensible role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons. Mol. Neurodegener., 2008, 3, 3.
105. Liu, Z., Wang, X.; Yu, Y.; Li, X.; Wang, T.; Jiang, H.; Ren, Q.; Jiao, Y.; Sawa, A.; Moran, T.; Ross, C.A.; Montell, C.; Smith, W.W. A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl. Acad. Sci. USA, 2008, 105, 2693-2698.
106. Sakaguchi-Nakashima, A.; Meir, J.Y.; Jin, Y.; Matsumoto, K.; Hisamoto, N. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr. Biol., 2007, 17, 592-598.
107. Wolozin, B.; Saha, S.; Guillily, M.; Ferree, A.; Riley, M. Investigating convergent actions of genes linked to familial Parkinson's disease. Neurodegener. Dis., 2008, 5, 182-185.
108. Saha, S.; Guillily, M.D.; Ferree, A.; Lanceta, J.; Chan, D.; Ghosh, J.; Hsu, C.H.; Segal, L.; Raghaven, K.; Matsumoto, K.; Hisamoto, N.; Kuwahara, T.; Iwatsubo, T.; Moore, L.; Goldstein, L.; Cookson, M.; Wolozin, B. LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans. J. Neurosci., 2009, 29, 9210-9218.
109. nd ed.; W.B. Saunders: London, 1996.
110. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is unstable on Huntington's disease chromosomes. Cell, 1993, 72, 971-983.
111. Sharp, A.H.; Loev, S.J.; Schilling, G.; Li, S.-H.; Li, X.-J.; Bao, J.; Wagster, M.V.; Kotzuk, J.A.; Stein, J.P.; Lo, A.; Hedreen, J.; Sisodia, S.; Snyder, S.H.; Dawson, T.M.; Ryugo, D.K.; Ross, C.A. Widespread expression of Huntington's disease gene (IT15) protein product. Neuron, 1995, 14, 1065-1074.
112. Vonsattel, J.P.; DiFiglia, M. Huntington disease. J. Neuropathol. Exp. Neurol., 1998, 57, 369-384.
113. Telenius, H.; Kremer, H.P.H.; Theilmann, J.; Andrew, S.E.; Almqvist, E.; Anvret, M.; Greenberg, C.; Greenberg, J.; Lucotte, G.; Squitieri, F.; Starr, A.; Goldberg, Y.P.; Hayden, M.R. Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n repeat length is the sex of the affected parent. Hum. Mol. Genet., 1993, 2, 1535-1540.
114. Wexler, N.S.; Young, A.B., Tanzi, R.E.; Travers, H.; Starosta-Rubinstein, S.; Penney, J.B.; Snodgrass, R.S.; Shoulson, I.; Gomez, F.; Ramos Arroyo, M.A.; Penchaszadeh, G.K.; Moreno, H.; Gibbons, K.; Faryniarz, A.; Hobbs, W.; Anderson, M.A.; Bonilla, E.; Conneally, P.M.; Gusella, J.F. Homozygotes for Huntington's disease. Nature, 1987, 326, 194-197.
115. Myers, R.H.; Leavitt, J.; Farrer, L.A.; Jagadeesh, J.; McFarlane, H.; Mastromauro, C.A.; Mark, R.J.; Gusella, J.F. Homozygote for Huntington disease. Am. J. Hum. Genet., 1989, 45, 615-618.
116. Strong, T.V.; Tagle, D.A.; Valdes, J.M.; Elmer, L.W.; Boehm, K.; Swaroop, M.; Kaatz, K.W.; Collins, F.S.; Albin, R.L. Widespread expression of the human and rat Huntington's disease gene in brain and nonneuronal tissues. Nat. Genet., 1993, 5, 259-263.
117. Rosas, H.D.; Koroshetz, W.J.; Chen, Y.I.; Skeuse, C.; Vangel, M.; Cudkowicz, M.E.; Caplan, K.; Marek, K.; Seidman, L.J.; Makris, N.; Jenkins, B.G.; Goldstein, J.M. Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology, 2003, 60, 1615-1620.
118. Jou, Y.-S.; Meyers, R.M. Evidence from antibody studies that the CAG repeat in the Huntington disease gene is expressed in the protein. Hum. Mol. Genet., 1995, 4, 465-469.
119. Trottier, Y.; Devys, D.; Imbert, G.; Sandou, F.; An, I.; Lutz, Y.; Weber, C.; Agid, Y.; Hirsch, E.C.; Mandel, J.-L. Cellular localisation of the Huntington's disease protein and discrimination of the normal and mutant forms. Nat. Genet., 1995, 10, 104-110.
120. La Spada, A.R.; Wilson, E.M.; Lubahn, D.B.; Harding, A.E.; Fischbeck, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature, 1991, 352, 77-79.
121. Orr, H.T.; Chung, M.; Banfi, S.; Kwiatkowski, T.J. Jr.; Servadio, A.; Beaudet, A.L.; McCall, A.E.; Duvick, L.A.; Ranum, L.P.W.; Zoghbi, H.Y. Expansion of an uns trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat. Genet., 1993, 4, 221-226.
122. Lindblad, K.; Savontaus, M.-L.; Stevanin, G.; Holmberg, M.; Digre, K.; Zander, C.; Ehrsson, H.; David, G.; Benomar, A.; Nikoskelainen, E.; Trottier, Y.; Holmgren, G.; Ptacek, L.J.; Anttinen, A.; Brice, A.; Schalling, M. An expanded CAG repeat sequence in spinocerebellar ataxia type 7. Gen. Res., 1996, 6, 965-971.
123. Zhuchenko, O.; Bailey, J.; Bonnen, P.; Ashizawa, T.; Stockton, D.W.; Amos, C.; Dobyns, W.B.; Subramony, S.H.; Zoghbi, H.Y.; Lee, C.C. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channel. Nat. Genet., 1997, 15, 62-69.
124. Koide, R.; Ikeuchi, T.; Onodera, O.; Tanaka, H.; Igarashi, S.; Endo, K.; Takahashi, H.; Kondo, R.; Ishikawa, A.; Hayashi, T.; Saito, M.; Tomoda, A.; Miike, T.; Naito, H.; Ikuta, F.; Tsuji, S. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat. Genet., 1994, 6, 9-13.
125. Kawaguchi, Y.; Okamoto, T.; Taniwaki, M.; Aizawa, M.; Inoue, M.; Katayama, S.; Kawakami, H.; Nakamura, S.; Nishimura, M.; Akiguchi, I.; Kimura, J.; Narumiya, S.; Kakizuka, A. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature, 1994, 8, 221-228.
126. Servadio, A.; Koshy, B.; Armstrong, D.; Antalffy, B.; Orr, H.T.; Zoghbi, H.Y. Expression of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals. Nat. Genet., 1995, 10, 94-98.
127. Yazawa, I.; Nukina, N.; Hashida, H.; Goto, J.; Yamada, M.; Kanazawa, I. Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain. Nat. Genet., 1995, 10, 99-103.
128. Vonsattel J.-P.; Myers, R.H.; Stevens, T.J.; Ferrante, R.J.; Bird, E.D.; Richardson, E.P. Jr. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol., 1985, 44, 559-577.
129. Kennedy, W.R.; Alter, M.; Sung, J.H. Progressive proximal spinal and bulbar atrophy of late onset: a sex linked recessive trait. Neurology, 1968, 18, 671-680.
130. Zoghbi, H.Y. Current Neurology; Appel, S.H., Ed.; Mosby-Year Book: St. Louis, 1993; pp. 87-110.
131. Dürr, A.; Stevanin, G.; Cancel, G.; Duyckaerts, C.; Abbas, N.; Didierjean, O.; Chneiweiss, H.; Benomar, A.; Lyon-Caen, O.; Julien, J.; Serdaru, M.; Penet, C.; Agid, Y.; Brice, A. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular and neuropathological features. Ann. Neurol., 1996, 39, 490-499.
132. Takahashi, H.; Ohama, E.; Naito, H.; Takeda, S.; Nakashima, S.; Makifuchi, T.; Ikuta, F. Hereditary dentatorubral-pallidoluysian atrophy: clinical and pathological variants in a family. Neurology, 1988, 38, 1065-1070.
133. DiFiglia, M.; Sapp, E.; Chase, K.; Schwarz, C.; Meloni, A.; Young, C.; Martin, E.; Vonsattel, J.-P.; Carraway, R.; Reeves, S.A.; Boyce, F.M.; Aronin, N. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron, 1995, 14, 1075-1081.
134. Qin, Z.-H.; Wang, Y.; Sapp, E.; Cuiffo, B.; Wanker, E.; Hayden, M.R.; Kegel, K.B.; Aronin, N.; DiFiglia, M. Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J. Neurosci., 2004, 24, 269-281.
135. Landles, C.; Bates, G.P. Huntingtin and the molecular pathogenesis of Huntington's disease. EMBO Rep., 2004, 5, 958-963.
136. Barnes G.T.; Duyao, M.P.; Ambrose, C.M.; McNeil, S.; Persichetti, F.; Srinidhi, J.; Gusella, J.F.; MacDonald, M.E. Mouse Huntington's disease gene homolog (Hdh). Somat. Cell Mol. Genet., 1993, 20, 87-97.
137. Mangiarini, L.; Sathasivam, K.; Seller, M.; Cozens, B.; Harper, A.; Hetherington, C.; Lawton, M.; Trottier, Y.; Lehrach, H.; Davies, S.W.; Bates, G.P. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 1996, 87, 493-506.
138. Carter, R.J.; Lione, L.A.; Humby, T.; Mangiarini, L.; Mahal, A.; Bates, G.P.; Dunnett, S.B.; Morton, A.J. Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci., 1999, 19, 3248-3257.
139. Lüesse, H.G.; Schiefer, J.; Spruenken, A.; Puls, C.; Block, F.; Kosinski, C.M. Evaluation of R6/2 HD transgenic mice for therapeutic studies in Huntington's disease: behavioural testing and impact of diabetes mellitus. Behav. Brain Res., 2001, 126, 185-195.
140. Bolivar, V.J.; Manley, K.; Messer, A. Exploratory and fear conditioning abnormalities develop early in R6/2 Huntington's disease transgenic mice. Behav. Neurosci., 2003, 117, 1233-1242.
141. Lione, L.A.; Carter, R.J.; Hunt, M.J.; Bates, G.P.; Morton, A.J.; Dunnett, S.B. Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J. Neurosci., 1999, 19, 10428-10437.
142. Murphy, K.P.S.J.; Carter, R.J.; Lione, L.A.; Mangiarini, L.; Mahal, A.; Bates, G.P.; Dunnett, S.B.; Morton, A.J. Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease gene. J. Neurosci., 2000, 20, 5115-5123.
143. Davies, S.W.; Turmaine, M.; Cozens, B.A.; DiFiglia, M.; Sharp, A.H.; Ross, C.A.; Scherzinger, E.; Wanker, E.E.; Mangiarini, L.; Bates, G.P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 1997, 90, 537-548.
144. Li, H.; Li, S.-H.; Cheng, A.L.; Mangiarini, L.; Bates, G.P.; Li, X.-J. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum. Mol. Genet., 1999, 8, 1227-1236.
145. Cha, J.-H.J. Transcriptional dysregulation in Huntington's disease. Trends Neurosci., 2000, 23, 387-392.
146. Cha, J.-H.J.; Kosinski, C.M.; Kerner, J.A.; Alsdorf, S.A.; Mangiarini, L.; Davies, S.W.; Penney, J.B.; Bates, C.P.; Young, A.B. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene. Proc. Natl. Acad. Sci. USA, 1998, 95, 6480-6485.
147. Luthi-Carter, R.; Strand, A.; Peters, N.L.; Solano, S.M.; Hollingsworth, Z.R.; Menon, A.S.; Frey, A.S.; Spektor, B.S.; Penney, E.B.; Schilling, G.; Ross, C.A.; Borchelt, D.R.; Tapscott, S.J.; Young, A.B.; Cha, J.-H.J.; Olson, J.M. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol. Genet., 2000, 9, 1259-1271.
148. Luthi-Carter, R.; Hanson, S.A.; Strand, A.D.; Bergstrom, D.A.; Chun, W.; Peters, N.L.; Woods, A.M.; Chan, E.Y.; Kooperberg, C.; Krainc, D.; Young, A.B.; Tapscott, S.J.; Olson, J.M. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum.Mol. Genet., 2002, 11, 1911-1926.
149. Zucker, B.; Luthi-Carter, R.; Kama, J.A.; Dunah, A.W.; Stern, E.A.; Fox, J.H.; Standaert, D.G.; Young, A.B.; Augood, S.J. Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1. Hum. Mol. Genet., 2005, 14, 179-189.
150. Björkqvist, M.; Fex, M.; Renström, E.; Wierup, N.; Petersén, Å.; Gil, J.; Bacos, K.; Popovic, N.; Li, J.-Y.; Sundler, F.; Brundin, P.; Mulder, H. The R6/2 transgenic mouse model of Huntington's disease develops diabetes due to deficient -cell mass. Hum. Mol. Genet., 2005, 14, 565-574.
151. Hurlbert, M.S.; Zhou, W.; Wasmeier, C.; Kaddis, F.G.; Hutton, J.C.; Freed, C.R. Mice transgenic for an expaneded CAG repeat in the Huntington's disease gene develop diabetes. Diabetes, 1999, 48, 649-651.
152. Podolsky, S.; Leopold, N.A.; Sax, D.S. Increased frequency of diabetes mellitus in patients with Huntington's chorea. Lancet, 1972, 1, 1356-1358.
153. Farrer, L.A. Diabetes mellitus in Huntington disease. Clin. Genet., 1985, 27, 62-67.
154. Björkqvist, M.; Petersén, Å.; Bacos, K.; Isaacs, J.; Norlén, P.; Gil, P.; Popovic, N.; Sundler, F.; Bates, G.P.; Tabrizi, S.J.; Brundin, P.; Mulder, H. Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2 transgenic mouse model of Huntington's disease. Hum. Mol. Genet., 2006, 15, 1713-1721.
155. Gil, J.M.; Mohapel, P.; Araújo, I.M.; Popovic, N.; Li, J.-Y.; Brundin, P.; Petersén, Å. Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice. Neurobiol. Dis., 2005, 20, 744-751.
156. Lazic, S.E.; Grote, H.; Armstrong, R.J.; Blakemore, C.; Hannan, A.J.; van Dellen, A.; Barker, R.A. Decreased hippocampal cell proliferation in R6/1 Huntington's mice. Neuroreport, 2004, 15, 811-813.
157. Turmaine, M.; Raza, A.; Mahal, A.; Mangiarini, L.; Bates, G.P.; and Davies, S.W. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc. Natl. Acad. Sci. USA, 2000, 97, 8093-8097.
158. Petersén, Å.; Gil, J.; Maat-Schieman, M.L.; Björkqvist, M.; Tanila, H.; Araújo, I.M.; Smith, R.; Popovic, N.; Wierup, N.; Norlén, P.; Li, J.-Y.; Roos, R.A.C.; Sundler, F.; Mulder, H.; Brundin, P. Orexin loss in Huntington's disease. Hum. Mol. Genet., 2005, 14, 39-47.
159. Morton, A.J.; Wood, N.I.; Hastings, M.H.; Hurelbrink, C.; Barker, R.A.; Maywood, E.S. Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. J. Neurosci., 2005, 25, 157-163.
160. Helmlinger, D.; Yvert, G.; Picaud, S.; Merienne, K.; Sahel, J.; Mandel, J.-L.; Devys, D. Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice. Hum. Mol. Genet., 2002, 11, 3351-3359.
161. Schilling G.; Becher, M.W.; Sharp, A.H.; Jinnah, H.A.; Duan, K.; Kotzuk, J.A.; Slunt, H.H.; Ratovitski, T.; Cooper, J.K.; Jenkins, N.A.; Copeland, N.G.; Price, D.L.; Ross, C.A.; Borchelt, D.R. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet., 1999, 8, 397-407.
162. Levine, M.S.; Klapstein, G.J.; Koppel, A.; Gruen, E.; Cepeda, C.; Vargas, M.E.; Jokel, E.S.; Carpenter, E.M.; Zanjani, H.; Hurst, R.S.; Efstratiadis, A.; Zeitlin, S.; Chesselet, M.-F. Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knock-in mouse models of Huntington's disease. J. Neurosci. Res., 1999, 58, 515-532.
163. DiFiglia, M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci., 1990, 13, 286-289.
164. Morton, A.J.; Leavens, W. Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res. Bull., 2000, 52, 51-59.
165. Hansson, O.; Petersén, Å.; Leist, M.; Nicotera, P.; Castilho, R.F. Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. Proc. Natl. Acad.Sci. USA, 1999, 96, 8727-8732.
166. Bogdanov, M.B.; Andreassen, O.A.; Dedeoglu, A.; Ferrante, R.J.; Beal, M.F. Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease. J. Neurochem., 2001, 79, 1246-1249.
167. Santamaría, A.; Peréz-Severiano, F.; Rodríguez-Martínez, E.; Maldonado, P.D.; Pedraza-Chaverri, J.; Rios, C.; Segovia, J. Comparative analysis of superoxide dismutase activity between acute pharmacological models and a transgenic mouse model of Huntington's disease. Neurochem. Res., 2001, 26, 419-424.
168. Tabrizi, S.J.; Workman, J.; Hart, P.E.; Mangiarini, L.; Mahal, A.; Bates, G.; Cooper, J.M.; Schapira, A.H. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann. Neurol., 2000, 47, 80-86.
169. Pérez-Severiano, F.; Escalante, B.; Vergara, P.; Rios, C.; Segovia, J. Age-dependent changes in nitric oxide synthase activity and protein expression in striata of mice transgenic for the Huntington's disease mutation. Brain Res., 2002, 951, 36-42.
170. Petersén, Å.; Larsen, K.E.; Behr, G.G.; Romero, N.; Przedborski, S.; Brundin, P.; Sulzer, D. Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration. Hum. Mol. Genet., 2001, 10, 1243-1254.
171. Reddy, P.H.; Williams, M.; Charles, V.; Garrett, L.; Pike-Buchanan, L.; Whetsell, W.O. Jr.; Miller, G.; Tagle, D.A. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat. Genet., 1998, 20, 198-202.
172. Hodgson, J.G.; Smith, D.J.; McCutcheon, K.; Koide, H.B.; Nishiyama, K.; Dinulos, M.B.; Stevens, M.E.; Bissada, N.; Nasir, J.; Kanazawa, I.; Disteche, C.M.; Rubin E.M.; Hayden, M.R. Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype. Hum. Mol. Genet., 1996, 5, 1875-1885.
173. Hodgson, J.G.; Agopyan, N.; Gutekunst, C.-A.; Leavitt, B.R.; LePiane, F.; Singaraja, R.; Smith, D.J.; Bissada, N.; McCutcheon, K.; Nasir, J.; LePiane, F.; Singaraja, R.; Smith, D.J.; Bissada, N.; McCutcheon, K.; Nasir, J.; Jamot, L.; Li, X.J.; Stevens, M.E.; Rosemond, E.; Roder, J.C.; Phillips, A.G.; Rubin, E.M.; Hersch, S.M.; Hayden, M.R. A YAC mouse model for Huntington's disease with full-length huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron, 1999, 23, 181-192.
174. Slow, E.J.; van Raamsdonk, J.; Rogers, D.; Coleman, S.H.; Graham, R.K.; Deng, Y.; Oh, R.; Bissada, N.; Hossain, S.M.; Yang, Y.-Z.; Li, X.-J.; Simpson, E.M.; Gutekunst, C.-A.; Leavitt, B.R.; Hayden, M.R. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum. Mol. Genet., 2003, 12, 1555-1567.
175. Van Raamsdonk, J.M.; Pearson, J.; Slow, E.J.; Hossain, S.M.; Leavitt, B.R.; Hayden, M.R. Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease. J. Neurosci., 2005, 25, 4169-4180.
176. Van Raamsdonk, J.M.; Warby, S.C.; Hayden, M.R. Selective degeneration in YAC mouse models of Huntington disease. Brain Res. Bull., 2007, 72, 124-131.
177. Gray, M.; Shirasaki, D.I.; Cepeda, C.; André, V.M.; Wilburn, B.; Lu, X.-H.; Tao, J.; Yamazaki, I.; Li, S.-H.; Sun, Y.E.; Li, X.-J.; Levine, M.S.; Yang, X.W. Full-length huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J. Neurosci., 2008, 28, 6182-6195.
178. Ross, C.A. Huntington's disease: new paths to pathogenesis. Cell, 2004, 118, 4-7.
179. Graham, R.K.; Deng, Y.; Slow, E.J.; Haigh, B.; Bissada, N.; Lu, G.; Pearson, J.; Shehadeh, J.; Bertram, L.; Murphy, Z.; Warby, S.C.; Doty, C.N.; Roy, S.; Wellington, C.L.; Leavitt, B.R.; Raymond, L.A.; Nicholson, D.W.; Hayden, M.R. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell, 2006, 125, 1179-1191.
180. Kennedy, L.; Shelbourne, P.F. Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease? Hum. Mol. Genet., 2000, 9, 2539-2544.
181. Ishiguro, H.; Yamada, K.; Sawada, H.; Nishii, K.; Ichino, N.; Sawada, M.; Kurosawa, Y.; Matsushita, N.; Kobayashi, K.; Goto, J.; Hashida, N.; Masuda, N.; Kanazawa, I.; Nagatsu, T. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J. Neurosci. Res., 2001, 65, 289-297.
182. Shelbourne, P.F.; Keller-McGandy, C.; Bi, W.L.; Yoon, S.-R.; Dubeau, L.; Veitch, N.J.; Vonsattel, J.P.; Wexler, N.S. The US-Venezuela Collaborative Research Group; Arnheim, N.; Augood, S.J. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum. Mol. Genet., 2007, 16, 1133-1142.
183. Kovtun, I.V.; Liu, Y.; Bjoras, M.; Klungland, A.; Wilson, S.H.; McMurray, C.T. OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature, 2007, 447, 447-452.
184. Yamamoto, A.; Luca J.J.; Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell, 2000, 101, 57-66.
185. White J.K.; Auerbach, W.; Duyao, M.P.; Vonsattel, J.-P.; Gusella, J.F.; Joyner, A.L.; MacDonald, M.E. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat. Genet., 1997, 17, 404-410.
186. Q111 knock-in mice. Hum. Mol. Genet., 2000, 9, 503-513.
187. Shelbourne, P.F.; Killeen, N.; Hevner, R.F.; Johnston, H.M.; Tecott, L.; Lewandoski, M.; Ennis, M.; Ramirez, L.; Li, Z.; Iannicola, C.; Littman, D.R.; Myers, R.M. Huntington's disease CAG expansion at the mouse Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol. Genet., 1999, 8, 763-774.
188. Lin, C.-H.; Tallaksen-Greene, S.; Chien, W.-M.; Cearley, J.A.; Jackson, W.S.; Crouse, A.B.; Ren, S.; Li, X.-J.; Albin, R.L.; Detloff, P.J. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mol. Genet., 2001, 10, 137-144.
189. Menalled, L.B.; Sison, J.D.; Wu, Y.; Olivieri, M.; Li, X.-J.; Li, H.; Zeitlin, S.; Chesselet, M.-F. Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J. Neurosci., 2002, 22, 8266-8276.
190. Li, H.; Li, S.-H.; Johnston, H.; Shelbourne, P.F.; Li, X.-J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet., 2000, 25, 385-389.
191. Menalled, L., Zanjania, H.; MacKenziea, L.; Koppelb, A.; Carpenterb, E.; Zeitlinc, S.; Chesselet, M.-F. Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease. Exp. Neurol., 2000, 162, 328-342.
192. Smith, M.A.; Brandt, J.; Shadmehr, R. Motor disorder in Huntington's disease begins as a dysfunction in error feedback control. Nature, 2000, 403, 544-549.
193. Szebenyi, G., Morfini, G.A.; Babcock, A.; Gould, M.; Selkoe, K.; Stenoien, D.L.; Young, M.; Faber, P.W.; MacDonald, M.E.; McPhaul, M.J.; Brady, S.T. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron, 2003, 40, 41-52.
194. Trushina, E.; Dyer, R.B.; Badger, J.D. II.; Ure, D.; Eide, L.; Tran, D.D.; Vrieze, B.T.; Legendre-Guillemin, V.; McPherson, P.S.; Mandavilli, B.S.; Van Houten, B.; Zeitlin, S.; McNiven, M.; Aebersold, R.; Hayden, M.; Parisi, J.E.; Seeberg, E.; Dragatsis, I.; Doyle, K.; Bender, A.; Chacko, C.; McMurray, C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol., 2004, 24, 8195-8209.
195. Morfini, G.; Pigino, G.; Brady, S.T. Polyglutamine expansion diseases: failing to deliver. Trends Mol. Med., 2005, 11, 64-70.
196. Morfini, G.A.; You, Y.-M.; Pollema, S.L.; Kaminska, A.; Liu, K.; Yoshioka, K.; Björkblom, B.; Coffey, E.T.; Bagnato, C.; Han, D.; Huang, C.-F.; Banker, G.; Pigino, G.; Brady, S.T. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat. Neurosci., 2009, 12, 864-871.
197. Maragakis, N.J; Rothstein, J.D. Glutamate transporters in neurologic disease. Arch. Neurol., 2001, 58, 365-370.
198. Lobsiger, C.S; Cleveland, D.W. Glial cells as intrinsic components of non-cellautonomous neurodegenerative disease. Nat. Neurosci., 2007, 10, 1355-1360.
199. Shin, J.-Y.; Fang, Z.H.; Yu, Z.-X.; Wang, C.-E.; Li, S.-H.; Li, X.-J. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J. Cell Biol., 2005, 171, 1001-1012.
200. Bradford, J.; Shin, J.-Y.; Roberts, M.; Wang, C.-E.; Li, X.-J.; Li, S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc. Natl. Acad. Sci. USA, 2009, 106, 22480-22485.
201. Lloret, A.; Dragileva, E.; Teed, A.; Espinola, J.; Fossale, E.; Gillis, T.; Lopez, E.; Myers, R.H.; MacDonald, M.E.; Wheeler, V.C. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice. Hum. Mol. Genet., 2006, 15, 2015-2024.
202. Van Raamsdonk, J.M.; Metzler, M.; Slow, E.; Pearson, J.; Schwab, C.; Carroll, J.; Graham, R.K.; Leavitt, B.R.; Hayden, M.R. Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain. Neurobiol. Dis., 2007, 26, 189-200.
203. Hockly, E.; Cordery, P.M.; Woodman, B.; Mahal, A.; van Dellen, A.; Blakemore, C.; Lewis, C.M.; Hannan, A.J.; Bates, G.P. Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann. Neurol., 2002, 51, 235-242.
204. Spires, T.L.; Grote, H.E.; Varshney, N.K.; Cordery, P.M.; van Dellen, A.; Blakemore, C.; Hannan, A.J. Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism. J. Neurosci., 2004, 24, 2270-2276.
205. van Dellen, A.; Cordery, P.M.; Spires, T.L.; Blakemore, C.; Hannan, A.J. Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease. BMC Neurosci., 2008, 9, 34.
206. Menalled, L.; El-Khodor, B.F.; Patry, M.; Suárez-Fariñas, M.; Orenstein, S.J., Zahasky, B.; Leahy, C.; Wheeler, V.; Yang, X.W.; MacDonald, M.; Morton, A.J.; Bates, G.; Leeds, J., Park, L.; Howland, D.; Signer, E.; Tobin, A.; Brunner, D. Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol. Dis., 2009, 35, 319-336.
207. Woodman, B.; Butler, R.; Landles, C.; Lupton, M.K.; Tse, J.; Hockly, E.; Moffitt, H.; Sathasivam, K.; Bates, G.P. The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. Brain Res. Bull., 2007, 72, 83-97.
208. Beal, M.F.; Ferrante, R.J. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat. Rev. Neurosci. 2004, 5, 373-384.
209. Handley, O.J.; Naji, J.J.; Dunnett, S.B.; Rosser, A.E. Pharmaceutical, cellular and genetic therapies for Huntington's disease. Clin. Sci. (Lond.), 2006, 110, 73-88.
210. Cooper, A.J.; Sheu, K.F.; Burke, J.R.; Strittmatter, W.J.; Gentile, V.; Peluso, G.; Blass, J.P. Pathogenesis of inclusion bodies in (CAG)n/Qn-expansion diseases with special reference to the role of tissue transglutaminase and to selective vulnerability. J. Neurochem., 1999, 72, 889-899.
211. Kahlem, P.; Green, H.; Djian, P. Transglutaminase action imitates Huntington's disease: selective polymerization of Huntingtin containing expanded polyglutamine. Mol. Cell, 1998, 1, 595-601.
212. Zainelli, G.M.; Dudek, N.L.; Ross, C.A.; Kim, S.Y.; Muma, N.A. Mutant huntingtin protein: a substrate for transglutaminase 1, 2, and 3. J. Neuropathol. Exp. Neurol., 2005, 64, 58-65.
213. Karpuj, M.V.; Garren, H.; Slunt, H.; Price, D.L.; Gusella, J.; Becher, M.W.; Steinman, L. Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei. Proc. Natl. Acad. Sci. USA, 1999, 96, 7388-7393.
214. Lesort, M.; Chun, W.; Johnson, G.V.W.; Ferrante, R.J. Tissue glutaminase is increased in Huntington's disease brain. J. Neurochem., 1999, 73, 2018-2027.
215. Mastroberardino, P.G.; Iannicola, C.; Nardacci, R.; Bernassola, F.; De Laurenzi, V.; Melino, G.; Moreno, S.; Pavone, F.; Oliverio, S.; Fesus, L.; Piacentini, M. 'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ., 2002, 9, 873-880.
216. Karpuj, M.V.; Becher, M.W.; Springer, J.E.; Chabas, D.; Youssef, S.; Pedotti, R.; Mitchell, D.; Steinman, L. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat. Med., 2002, 8, 143-149.
217. Bao, J.; Sharp, A.H.; Wagster, M.V.; Becher, M.; Schilling, G.; Ross, C.A.; Dawson, V.L.; Dawson, T.M. Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc. Natl. Acad. Sci. USA, 1996, 93, 5037-5042.
218. Zainelli, G.M.; Ross, C.A.; Troncoso, J.C.; Fitzgerald, J.K.; Muma, N.A. Calmodulin regulates transglutaminase 2 cross-linking of huntingtin. J. Neurosci., 2004, 24, 1954-1961.
219. Dudek, N.L.; Dai, Y.; Muma, N.A. Protective effects of interrupting the binding of calmodulin to mutant huntingtin. J. Neuropathol. Exp. Neurol., 2008, 67, 355-365.
220. Dai, Y.; Dudek, N.L.; Li, Q.; Fowler, S.C.; Muma, N.A. Striatal expression of a calmodulin fragment improved motor function, weight loss, and neuropathology in the R6/2 mouse model of Huntington's disease. J. Neurosci., 2009, 29, 11550-11559.
221. Khoshnan, A.; Ko, J.; Patterson, P.H. Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity. Proc. Natl. Acad. Sci. USA, 2002, 99, 1002-1007.
222. Zhou, C.; Emadi, S.; Sierks, M.R.; Messer, A. A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein. Mol. Ther., 2004, 10, 1023-1031.
223. Emadi, S.; Barkhordarian, H.; Wang, M.S.; Schulz, P.; Sierks, M.R. Isolation of a human single chain antibody fragment against oligomeric -synuclein that inhibits aggregation and prevents α-synuclein-induced toxicity. J. Mol. Biol., 2007, 368, 1132-1144.
224. Wolfgang, W.J.; Miller, T.W.; Webster, J.M.; Huston, J.S.; Thompson, L.M.; Marsh, J.L.; Messer, A. Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies. Proc. Natl. Acad. Sci. USA, 2005, 102, 11563-11568.
225. McLear, J.A.; Lebrecht, D.; Messer, A.; Wolfgang, W.J. Combinatorial approach of intrabody with enhanced Hsp70 expression addresses multiple pathologies in a fly model of Huntington's disease. FASEB J. 2008, 22, 2003-2011.
226. Southwell, A.L.; Khoshnan, A.; Dunn, D.E.; Bugg, C.W.; Lo, D.C.; Patterson, P.H. Intrabodies binding the praline-rich domains of mutant huntingtin increase its turnover and reduce neurotoxicity. J. Neurosci., 2008, 28, 9013-9020.
227. Colby, D.W.; Chu, Y.; Cassady, J.P.; Duennwald, M.; Zazulak, H.; Webster, J.M.; Messer, A.; Lindquist, S.; Ingram, V.M.; Wittrup, K.D. Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody. Proc. Natl. Acad. Sci. USA, 2004, 101, 17616-17621.
228. Wang, C.-E.; Zhou, H., McGuire, J.R.; Cerullo, V.; Lee, B.; Li, S.-H.; Li, X.-J. Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J. Cell Biol., 2008, 181, 803-816.
229. Southwell, A.L.; Ko, J.; Patterson, P.H. Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. J. Neurosci., 2009, 29, 13589-13602.
230. Menalled, L.B.; Chesselet, M.-F. Mouse models of Huntington's disease. Trends Pharmacol. Sci., 2002, 23, 32-39.
231. Gil, J.M.; Rego, A.C. The R6 lines of transgenic mice: a model for screening new therapies for Huntington's disease. Brain Res. Rev., 2008, 59, 410-431.
232. Okamoto, S.; Pouladi, M.A.; Talantova, M.; Yao, D.; Xia, P.; Ehrnhoefer, D.E.; Zaidi, R.; Clemente, A.; Kaul, M.; Graham, R.K.; Zhang, D.; Chen, H.-S.V.; Tong, G.; Hayden, M.R.; Lipton, S.A. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat. Med., 2009, 15, 1407-1413.
233. Crusio, W.E. Editorial: Troublesome variability in mouse studies. Nat. Neurosci., 2009, 12, 1075.