Modulation of energy deficiency in Huntington's disease via activation of the peroxisome proliferator-activated receptor gamma

Human Molecular Genetics

Volumn 19, Issue 20, 2010, Pages 4043-4058

  Chiang, Ming Chang ^a,b   Chen, Chiung Mei ^c   Lee, Maw Rong ^d   Chen, Hsiao Wen ^b   Chen, Hui Mei ^a   Wu, Yu Shuo ^a   Hung, Cheng Han ^d   Kang, Jheng Jie ^a   Chang, Ching Pang ^a   Chang, Chen ^a   Wu, Yih Ru ^c   Tsai, Yau Sheng ^e   Chern, Yijuang ^a  

^a INSTITUTE OF BIOMEDICAL SCIENCES   (Taiwan)

^b CHINESE CULTURE UNIVERSITY   (Taiwan)

^c CHANG GUNG UNIVERSITY COLLEGE OF MEDICINE   (Taiwan)

^d NATIONAL CHUNG HSING UNIVERSITY   (Taiwan)

^e NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 5 NITROBENZANILIDE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; BRAIN DERIVED NEUROTROPHIC FACTOR; GLUCOSE TRANSPORTER 4; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN BCL 2; ROSIGLITAZONE;

ADULT; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; CLINICAL ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; DOWN REGULATION; ENERGY METABOLISM; ENZYME ACTIVATION; GENE EXPRESSION; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; LYMPHOCYTE; MOUSE; MUTANT; NERVE CELL; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; UBIQUITINATION; WEIGHT REDUCTION;

ADIPOCYTES; ANIMALS; BRAIN; DOWN-REGULATION; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GLUCOSE TRANSPORTER TYPE 4; HUMANS; HUNTINGTON DISEASE; LIVER; LYMPHOCYTES; MICE; POLYMERASE CHAIN REACTION; PPAR GAMMA; THIAZOLIDINEDIONES; TRANS-ACTIVATORS;

MUS;

EID: 77957727491     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddq322     Document Type: Article

References (85)

1. Huntington's Disease Collaborative Research Group. (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell, 72, 971-983.
2. Vonsattel, J.P., Myers, R.H., Stevens, T.J., Ferrante, R.J., Bird, E.D. and Richardson, E.P. Jr (1985) Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol., 44, 559-577.
3. Reddy, P.H., Williams, M. and Tagle, D.A. (1999) Recent advances in understanding the pathogenesis of Huntington's disease. Trends Neurosci., 22, 248-255.
4. Waelter, S., Boeddrich, A., Lurz, R., Scherzinger, E., Lueder, G., Lehrach, H. and Wanker, E.E. (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell, 12, 1393-1407.
5. Jana, N.R., Tanaka, M., Wang, G.-H. and Nukina, N. (2000) Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet., 9, 2009-2018.
6. Suhr, S.T., Senut, M.C., Whitelegge, J.P., Faull, K.F., Cuizon, D.B. and Gage, F.H. (2001) Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J. Cell Biol., 153, 283-294.
7. Steffan, J.S., Kazantsev, A., Spasic-Boskovic, O., Greenwald, M., Zhu, Y.Z., Gohler, H., Wanker, E.E., Bates, G.P., Housman, D.E. and Thompson, L.M. (2000) The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci. USA, 97, 6763-6768.
8. Dunah, A.W., Jeong, H., Griffin, A., Kim, Y.M., Standaert, D.G., Hersch, S.M., Mouradian, M.M., Young, A.B., Tanese, N. and Krainc, D. (2002) Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science, 296, 2238-2243.
9. Chiang, M.C., Lee, Y.C., Huang, C.L. and Chern, Y. (2005) cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J. Biol. Chem., 280, 14331-14340.
10. Chiang, M.C., Chen, H.M., Lee, Y.H., Chang, H.H., Wu, Y.C., Soong, B.W., Chen, C.M., Wu, Y.R., Liu, C.S., Niu, D.M. et al. (2007) Dysregulation of C/EBPalpha by mutant Huntingtin causes the urea cycle deficiency in Huntington's disease. Hum. Mol. Genet., 16, 483-498.
11. Chiang, M.C., Chen, H.M., Lai, H.L., Chen, H.W., Chou, S.Y., Chen, C.M., Tsai, F.J. and Chern, Y. (2009) The A2A adenosine receptor rescues the urea cycle deficiency of Huntington's disease by enhancing the activity of the ubiquitin-proteasome system. Hum. Mol. Genet., 18, 2929-2942.
12. Podolsky, S., Leopold, N.A. and Sax, D.S. (1972) Increased frequency of diabetes mellitus in patients with Huntington's chorea. Lancet, 1, 1356-1358.
13. Underwood, B.R., Broadhurst, D., Dunn, W.B., Ellis, D.I., Michell, A.W., Vacher, C., Mosedale, D.E., Kell, D.B., Barker, R.A., Grainger, D.J. et al. (2006) Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles. Brain, 129, 877-886.
14. Valenza, M., Carroll, J.B., Leoni, V., Bertram, L.N., Bjorkhem, I., Singaraja, R.R., Di Donato, S., Lutjohann, D., Hayden, M.R. and Cattaneo, E. (2007) Cholesterol biosynthesis pathway is disturbed in YAC128 mice and is modulated by huntingtin mutation. Hum. Mol. Genet., 16, 2187-2198.
15. Rosen, E.D., Hsu, C.H., Wang, X., Sakai, S., Freeman, M.W., Gonzalez, F.J. and Spiegelman, B.M. (2002) C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev., 16, 22-26.
16. Quintanilla, R.A., Jin, Y.N., Fuenzalida, K., Bronfman, M. and Johnson, G.V. (2008) Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease. J. Biol. Chem., 283, 25628-25637.
17. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493-506.
18. Fajas, L., Auboeuf, D., Raspe, E., Schoonjans, K., Lefebvre, A.M., Saladin, R., Najib, J., Laville, M., Fruchart, J.C., Deeb, S. et al. (1997) The organization, promoter analysis, and expression of the human PPARgamma gene. J. Biol. Chem., 272, 18779-18789.
19. Walker, G.E., Marzullo, P., Verti, B., Guzzaloni, G., Maestrini, S., Zurleni, F., Liuzzi, A. and Di Blasio, A.M. (2008) Subcutaneous abdominal adipose tissue subcompartments: potential role in rosiglitazone effects. Obesity (Silver Spring), 16, 1983-1991.
20. Chou, S.Y., Lee, Y.C., Chen, H.M., Chiang, M.C., Lai, H.L., Chang, H.H., Wu, Y.C., Sun, C.N., Chien, C.L., Lin, Y.S. et al. (2005) CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. J. Neurochem., 93, 310-320.
21. Duan, W., Guo, Z., Jiang, H., Ware, M., Li, X.J. and Mattson, M.P. (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc. Natl Acad. Sci. USA, 100, 2911-2916.
22. Lalic, N.M., Maric, J., Svetel, M., Jotic, A., Stefanova, E., Lalic, K., Dragasevic, N., Milicic, T., Lukic, L. and Kostic, V.S. (2008) Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch. Neurol., 65, 476-480.
23. Bhatia, V. and Viswanathan, P. (2006) Insulin resistance and PPAR insulin sensitizers. Curr. Opin. Investig. Drugs, 7, 891-897.
24. Hurlbert, M.S., Zhou, W., Wasmeier, C., Kaddis, F.G., Hutton, J.C. and Freed, C.R. (1999) Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes. Diabetes, 48, 649-651.
25. Chou, C.C., Lee, M.R., Cheng, F.C. and Yang, D.Y. (2005) Solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry for determination of trace rosiglitazone in urine. J. Chromatogr. A, 1097, 74-83.
26. van Dellen, A., Blakemore, C., Deacon, R., York, D. and Hannan, A.J. (2000) Delaying the onset of Huntington's in mice. Nature, 404, 721-722.
27. Tsai, Y.S., Tsai, P.J., Jiang, M.J., Chou, T.Y., Pendse, A., Kim, H.S. and Maeda, N. (2009) Decreased PPAR gamma expression compromises perigonadal-specific fat deposition and insulin sensitivity. Mol. Endocrinol., 23, 1787-1798.
28. Aziz, N.A., van der Burg, J.M., Landwehrmeyer, G.B., Brundin, P., Stijnen, T. and Roos, R.A. (2008) Weight loss in Huntington disease increases with higher CAG repeat number. Neurology, 71, 1506-1513.
29. Fain, J.N., Del Mar, N.A., Meade, C.A., Reiner, A. and Goldowitz, D. (2001) Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation. Hum. Mol. Genet., 10, 145-152.
30. Phan, J., Hickey, M.A., Zhang, P., Chesselet, M.F. and Reue, K. (2009) Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models. Hum. Mol. Genet., 18, 1006-1016.
31. Hondares, E., Mora, O., Yubero, P., Rodriguez de la Concepcion, M., Iglesias, R., Giralt, M. and Villarroya, F. (2006) Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation. Endocrinology, 147, 2829-2838.
32. Armoni, M., Kritz, N., Harel, C., Bar-Yoseph, F., Chen, H., Quon, M.J. and Karnieli, E. (2003) Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect. J. Biol. Chem., 278, 30614-30623.
33. Puigserver, P. and Spiegelman, B.M. (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev., 24, 78-90.
34. Lehrke, M. and Lazar, M.A. (2005) The many faces of PPARgamma. Cell, 123, 993-999.
35. Liu, M.L., Gibbs, E.M., McCoid, S.C., Milici, A.J., Stukenbrok, H.A., McPherson, R.K., Treadway, J.L. and Pessin, J.E. (1993) Transgenic mice expressing the human GLUT4/muscle-fat facilitative glucose transporter protein exhibit efficient glycemic control. Proc. Natl Acad. Sci. USA, 90, 11346-11350.
36. Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R.C. et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 98, 115-124.
37. Pagel-Langenickel, I., Bao, J., Joseph, J.J., Schwartz, D.R., Mantell, B.S., Xu, X., Raghavachari, N. and Sack, M.N. (2008) PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle. J. Biol. Chem., 283, 22464-22472.
38. Wilson-Fritch, L., Burkart, A., Bell, G., Mendelson, K., Leszyk, J., Nicoloro, S., Czech, M. and Corvera, S. (2003) Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol. Cell. Biol., 23, 1085-1094.
39. Guan, H.P., Ishizuka, T., Chui, P.C., Lehrke, M. and Lazar, M.A. (2005) Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes. Genes Dev., 19, 453-461.
40. Ross, C.A. and Pickart, C.M. (2004) The ubiquitin-proteasome pathway in Parkinson's disease and other neurodegenerative diseases. Trends Cell Biol., 14, 703-711.
41. Nandi, D., Tahiliani, P., Kumar, A. and Chandu, D. (2006) The ubiquitin-proteasome system. J. Biosci., 31, 137-155.
42. Bennett, E.J., Shaler, T.A., Woodman, B., Ryu, K.Y., Zaitseva, T.S., Becker, C.H., Bates, G.P., Schulman, H. and Kopito, R.R. (2007) Global changes to the ubiquitin system in Huntington's disease. Nature, 448, 704-708.
43. Domingues, A.F., Arduino, D.M., Esteves, A.R., Swerdlow, R.H., Oliveira, C.R. and Cardoso, S.M. (2008) Mitochondria and ubiquitin-proteasomal system interplay: relevance to Parkinson's disease. Free Radic. Biol. Med., 45, 820-825.
44. Zhang, Y., Ona, V.O., Li, M., Drozda, M., Dubois-Dauphin, M., Przedborski, S., Ferrante, R.J. and Friedlander, R.M. (2003) Sequential activation of individual caspases, and of alterations in Bcl-2 proapoptotic signals in a mouse model of Huntington's disease. J. Neurochem., 87, 1184-1192.
45. Duan, W., Peng, Q., Masuda, N., Ford, E., Tryggestad, E., Ladenheim, B., Zhao, M., Cadet, J.L., Wong, J. and Ross, C.A. (2008) Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease. Neurobiol. Dis., 30, 312-322.
46. Butts, B.D., Tran, N.L. and Briehl, M.M. (2004) Identification of a functional peroxisome proliferator activated receptor response element in the 3′ untranslated region of the human bcl-2 gene. Int. J. Oncol., 24, 1305-1310.
47. Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B.R., Goffredo, D., Conti, L., MacDonald, M.E., Friedlander, R.M., Silani, V., Hayden, M.R. et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science, 293, 493-498.
48. Sundararajan, S., Jiang, Q., Heneka, M. and Landreth, G. (2006) PPARgamma as a therapeutic target in central nervous system diseases. Neurochem. Int., 49, 136-144.
49. Landreth, G. (2006) PPARgamma agonists as new therapeutic agents for the treatment of Alzheimer's disease. Exp. Neurol., 199, 245-248.
50. Bordet, R., Ouk, T., Petrault, O., Gele, P., Gautier, S., Laprais, M., Deplanque, D., Duriez, P., Staels, B., Fruchart, J.C. et al. (2006) PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases. Biochem. Soc. Trans., 34, 1341-1346.
51. Lazar, M.A. (2005) PPAR gamma, 10 years later. Biochimie, 87, 9-13.
52. Fuenzalida, K., Quintanilla, R., Ramos, P., Piderit, D., Fuentealba, R.A., Martinez, G., Inestrosa, N.C. and Bronfman, M. (2007) Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J. Biol. Chem., 282, 37006-37015.
53. Wu, J.S., Lin, T.N. and Wu, K.K. (2009) Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins. J. Cell. Physiol., 220, 58-71.
54. Ferrante, R.J., Andreassen, O.A., Jenkins, B.G., Dedeoglu, A., Kuemmerle, S., Kubilus, J.K., Kaddurah-Daouk, R., Hersch, S.M. and Beal, M.F. (2000) Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci., 20, 4389-4397.
55. Li, M., Huang, Y., Ma, A.A., Lin, E. and Diamond, M.I. (2009) Y-27632 improves rotarod performance and reduces huntingtin levels in R6/2 mice. Neurobiol. Dis., 36, 413-420.
56. Van Raamsdonk, J.M., Pearson, J., Rogers, D.A., Lu, G., Barakauskas, V.E., Barr, A.M., Honer, W.G., Hayden, M.R. and Leavitt, B.R. (2005) Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease. Exp. Neurol., 196, 266-272.
57. Van Raamsdonk, J.M., Pearson, J., Bailey, C.D., Rogers, D.A., Johnson, G.V., Hayden, M.R. and Leavitt, B.R. (2005) Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease. J. Neurochem., 95, 210-220.
58. Nance, M.A. and Sanders, G. (1996) Characteristics of individuals with Huntington disease in long-term care. Mov. Disord., 11, 542-548.
59. Myers, R.H., Sax, D.S., Koroshetz, W.J., Mastromauro, C., Cupples, L.A., Kiely, D.K., Pettengill, F.K. and Bird, E.D. (1991) Factors associated with slow progression in Huntington's disease. Arch. Neurol., 48, 800-804.
60. Trayhurn, P., Bing, C. and Wood, I.S. (2006) Adipose tissue and adipokines-energy regulation from the human perspective. J. Nutr., 136, 1935S-1939S.
61. Rosen, E.D., Walkey, C.J., Puigserver, P. and Spiegelman, B.M. (2000) Transcriptional regulation of adipogenesis. Genes Dev., 14, 1293-1307.
62. Spiegelman, B.M. (1998) PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes, 47, 507-514.
63. Tsai,Y.S. and Maeda, N. (2005) PPARgamma: a critical determinant of body fat distribution in humans and mice. Trends Cardiovasc. Med., 15, 81-85.
64. He, W., Barak, Y., Hevener, A., Olson, P., Liao, D., Le, J., Nelson, M., Ong, E., Olefsky, J.M. and Evans, R.M. (2003) Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc. Natl Acad. Sci. USA, 100, 15712-15717.
65. Shepherd, P.R. and Kahn, B.B. (1999) Glucose transporters and insulin action-implications for insulin resistance and diabetes mellitus. N. Engl. J. Med., 341, 248-257.
66. Minokoshi, Y., Kahn, C.R. and Kahn, B.B. (2003) Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J. Biol. Chem., 278, 33609-33612.
67. Hammarstedt, A., Andersson, C.X., Rotter Sopasakis, V. and Smith, U. (2005) The effect of PPARgamma ligands on the adipose tissue in insulin resistance. Prostaglandins Leukot. Essent. Fatty Acids, 73, 65-75.
68. Cui, L., Jeong, H., Borovecki, F., Parkhurst, C.N., Tanese, N. and Krainc, D. (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 127, 59-69.
69. Weydt, P., Pineda, V.V., Torrence, A.E., Libby, R.T., Satterfield, T.F., Lazarowski, E.R., Gilbert, M.L., Morton, G.J., Bammler, T.K., Strand, A.D. et al. (2006) Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab., 4, 349-362.
70. Taherzadeh-Fard, E., Saft, C., Andrich, J., Wieczorek, S. and Arning, L. (2009) PGC-1alpha as modifier of onset age in Huntington disease. Mol. Neurodegener., 4, 10.
71. Chaturvedi, R.K., Adhihetty, P., Shukla, S., Hennessy, T., Calingasan, N., Yang, L., Starkov, A., Kiaei, M., Cannella, M., Sassone, J. et al. (2009) Impaired PGC-1alpha function in muscle in Huntington's disease. Hum. Mol. Genet., 18, 3048-3065.
72. Sherman, M.Y. and Goldberg, A.L. (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron, 29, 15-32.
73. Sun, F., Kanthasamy, A., Anantharam, V. and Kanthasamy, A.G. (2007) Environmental neurotoxic chemicals-induced ubiquitin proteasome system dysfunction in the pathogenesis and progression of Parkinson's disease. Pharmacol. Ther., 114, 327-344.
74. van Tijn, P., Hol, E.M., van Leeuwen, F.W. and Fischer, D.F. (2008) The neuronal ubiquitin-proteasome system: murine models and their neurological phenotype. Prog. Neurobiol., 85, 176-193.
75. Mestre, T., Ferreira, J., Coelho, M.M., Rosa, M. and Sampaio, C. (2009) Therapeutic interventions for disease progression in Huntington's disease. Cochrane Database Syst. Rev., CD006455.
76. Hunt, M.J. and Morton, A.J. (2005) Atypical diabetes associated with inclusion formation in the R6/2 mouse model of Huntington's disease is not improved by treatment with hypoglycaemic agents. Exp. Brain Res., 166, 220-229.
77. Lee, M.J., Chang, C.P., Lee, Y.H., Wu, Y.C., Tseng, H.W., Tung, Y.Y., Wu, M.T., Chen, Y.H., Kuo, L.T., Stephenson, D. et al. (2009) Longitudinal evaluation of an N-ethyl-N-nitrosourea-created murine model with normal pressure hydrocephalus. PLoS ONE, 4, e7868.
78. Ma, M., Basso, D.M., Walters, P., Stokes, B.T. and Jakeman, L.B. (2001) Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse. Exp. Neurol., 169, 239-254.
79. Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685.
80. Chiang, M.C., Juo, C.G., Chang, H.H., Chen, H.M., Yi, E.C. and Chern, Y. (2007) Systematic uncovering of multiple pathways underlying the pathology of Huntington disease by an acid-cleavable isotope-coded affinity tag approach. Mol. Cell Proteomics, 6, 781-797.
81. Wanker, E.E., Scherzinger, E.,Heiser, V.,Sittler,A., Eickhoff, H. andLehrach, H. (1999) Membrane filter assay for detection of amyloid-like polyglutaminecontaining protein aggregates. Methods Enzymol., 309, 375-386.
82. Liu, F.C., Wu, G.C., Hsieh, S.T., Lai, H.L., Wang, H.F., Wang, T.W. and Chern, Y. (1998) Expression of type VI adenylyl cyclase in the central nervous system: implication for a potential regulator of multiple signals in different neurotransmitter systems. FEBS Lett., 436, 92-98.
83. Ehrlich, M.E., Conti, L., Toselli, M., Taglietti, L., Fiorillo, E., Taglietti, V., Ivkovic, S., Guinea, B., Tranberg, A., Sipione, S., Rigamonti, D. and Cattaneo, E. (2001) ST14A cells have properties of a medium-size spiny neuron. Exp. Neurol., 167, 215-226.
84. Pendergrass, W., Wolf, N. and Poot, M. (2004) Efficacy of MitoTracker Green and CMXrosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry A, 61, 162-169.
85. Huntington Study Group. (1996) Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov. Disord., 11, 136-142.