A critical evaluation of adenosine A2A receptors as potentially "druggable" targets in Huntington's disease

Current Pharmaceutical Design

Volumn 14, Issue 15, 2008, Pages 1500-1511

  Popoli, Patrizia ^a   Blum, David ^b,c   Domenici, Maria Rosaria ^a   Burnouf, Sylvie ^b,c   Chen, Yijuang ^d  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b JEAN PIERRE AUBERT RESEARCH CENTER   (France)

^c UNIV LILLE   (France)

^d INSTITUTE OF BIOMEDICAL SCIENCES   (Taiwan)

Author keywords

Adenosine A2A receptors; BDNF; Dopamine; Excitotoxicity; Experimental models; Heterodimers; Huntington's disease; Mitochondrial dysfunction

Indexed keywords

2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); 3 NITROPROPIONIC ACID; 3,7 DIMETHYL 1 PROPARGYLXANTHINE; 4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; 5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; 8 (3 CHLOROSTYRYL)CAFFEINE; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR AGONIST; ADENOSINE A2A RECEPTOR ANTAGONIST; ADENYLATE CYCLASE; AMINOPYRIDINE; BRAIN DERIVED NEUROTROPHIC FACTOR; DOPAMINE 2 RECEPTOR; GLUTAMIC ACID; HUNTINGTIN; ISTRADEFYLLINE; MSX 3; N [2 (4 BROMOCINNAMYLAMINO)ETHYL] 5 ISOQUINOLINESULFONAMIDE; YAC 128;

BRAIN ATROPHY; BRAIN DISEASE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG ADMINISTRATION ROUTE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG MEGADOSE; DRUG PENETRATION; DRUG TARGETING; GENE EXPRESSION; GENE FUNCTION; GENETIC ENGINEERING; GENETIC TRANSCRIPTION; GLIA CELL; HUMAN; HUNTINGTON CHOREA; INFLAMMATION; INTRASTRIATAL DRUG ADMINISTRATION; LOCOMOTION; LOW DRUG DOSE; METABOLIC DISORDER; MOTOR PERFORMANCE; NERVE DEGENERATION; NERVE EXCITABILITY; NEUROPROTECTION; NEUROTRANSMITTER RELEASE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STRIATE CORTEX;

EID: 47349089093     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161208784480117     Document Type: Review

References (196)

1. Harper P. Huntington's Disease. London, W. B. Saunders Co. 1991.
2. Ferrante RJ, Kowall NW, Beal MF, Martin JB, Bird ED, Richardson EP. Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease. J Neuropathol Exp Neurol 1987; 46: 12-27.
3. Mitchell IJ, Cooper AJ, Griffiths MR. The selective vulnerability of striatopallidal neurons. Prog Neurobiol 1999; 59: 691-719.
4. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72: 971-83.
5. Snell RG, MacMillem JC, Cheadle JP, Fenton I, Lazarou LP, Davies P, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat Genet 1993; 4: 393-97.
6. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackel E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington!s disease age of onset. Proc Nad Acad Sci USA 2004; 101: 3498-503.
7. Andresen JM, Gayán J, Djoussé L, Roberts S, Brocklebank D, Cherny SS, et al. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset. Ann Hum Genet 2007; 71: 295-301.
8. Bates G. Huntington's disease. Oxford, Oxford University Press 2002.
9. Trottier Y, Devys D, Imbert G, Saudou F, An I, Lutz Y, et al. Cellular localization of the Huntington's discase protein and discrimination of the normal and mutated form. Nat Genet 1995; 10: 104-10.
10. Gourfinkel-An I, Cancel G, Trottier Y, Devys D, Tora L, Lutz Y, et al. Differential distribution of the normal and mutated forms of huntingtin in the human brain. Ann Neurol 1997; 42: 712-9.
11. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ. Expression of mutant Huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005; 171: 1001-12.
12. Aronin N, Chase K, Young C, Sapp E, Schwarz C, Matta N, et al. CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain. Neuron 1995; 15: 1193-201.
13. Landwebrmeyer GB, McNeil SM, Dure LS 4th, Ge P, Aizawa H Huang Q, et al. Huntington's disease gene: Regional and cellular expression in brain of normal and affected individuals. Ann Neuro 1995; 37: 218-30
14. Sun Y, Savanenin A, Reddy PH, Liu YF. Polyglutamine-expanded Huntingtin promotes sensitization of N-methyl-D-aspartate receptors via post-synaptic density 95. J Biol Chem 2001; 276: 24713-8
15. Harjes P, Wanker EE. The hunt for huntingtin function: Interaction partners tell many different stories. Trends Biochem Sci 2003; 28 425-33.
16. Gauthier LR, Charrin BC, Borrell-Pagès M, Dompierre JP, Rangone H, Cordelières FP, et al. Huntingtin controls neurotrophi support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004; 118: 127-38.
17. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006; 127: 59-69.
18. Strehlow AN, Li JZ, Myers RM. Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space. Hum Mol Genet 2007; 16: 391-409.
19. Rigamonti D, Bauer JH, De-Fraja U, Conti L, Sipione S, Sciorati C, et al. Wild type Huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 2000; 20: 3705-13.
20. Rigamonti D, Sipione S, Goffredo D. Zuccato C, Fossale E, Cattaneo E. Huntingtin's neuroprotective activity occurs via inhibition of procaspase-9 processing. J Biol Chem 2001; 276: 14545-8.
21. Zhang Y, Leavitt BR, van Raamsdonk JM, Dragatsis I, Goldowitz D, MacDonald ME, et al. Huntingtin inhibits caspase-3 activation. EMBO J 2006; 25: 5896-906.
22. Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, et al. Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 1995; 269; 407-10.
23. Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, et al. Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 1995; 81: 811-23.
24. Zeitlin S, Liu JP, Chapman DL, Papaioamou VE, Efstratiadis A. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat Genet 1995; 11: 155-63.
25. Dragatsis I, Dietrich P, Zeitlin S. Expression of the Huntingtin-associated protein 1 gene in the developing and adult mouse. Neurosci Lett 2000; 282: 37-40.
26. Cattaneo E, Zuccato C, Tartari M. Normal Huntingtin function: An alternative approach to Huntingtons disease. Nat Rev Neurosci 2005; 6: 919-30.
27. Van Raamsdonk JM, Murphy Z, Slow EJ, Leavitt BR, Hayden MR. Selective Degeneration and Nuclear Localization of Mutant Huntingtin in the YAC128 Mouse Model of Huntington Disease. Hum Mol Genet 2005; 14: 3823-35.
28. Van Raamsdonk JM, Pearson J, Murphy Z, Hayden MR, Leavitt BR. Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease. BMC Neurosci 2006; 7: 80.
29. Stack EC, Ferrante RJ. Huntington's disease: Progress and potential in the field. Expert Opin Investig Drugs 2007; 12: 1933-53.
30. Truant R, Atwal RS, Burtnik A. Nucleocytoplasmic trafficking and transcription effects of huntingtin in Huntington's disease. Prog Neurobiol 2007;83: 211-27.
31. Fan MM and Raymond LA. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog Neurobiol 2007; 81: 272-93.
32. Li S, Li XJ. Multiple pathways contribute to the pathogenesis of Huntington disease. Mol Neurodegener 2006; 1: 19.
33. Brouillet E, Jacquard C, Bizat N, Blum D. 3-Nitropropionic acid: A mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease. J Neurochem 2005; 95: 1521-40.
34. Brouillet E, Conde F. Beal MF, Hantraye P. Replicating Huntington's disease phenotype in experimental animals. Prog Neurobiol 1999; 59:427-68.
35. Jacquard C, Trioulier Y, Cosker F, Escartin C, Bizat N, Hantraye P, et al. Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation. FASEB J 2006; 20: 1021-3.
36. Stack EC, Dedeoglu A, Smith KM, Cormier K, Kubilus JK, Bogdanov K, et al. Neuroprotective effects of synaptic modulation in Huntington's disease R6/2 mice. J Neurosci 2007; 27: 12908-15.
37. Liévens JC, Woodman B. Mahal A, Spasic-Boscovic O, Samuel D, Kerkerian-Le Goff L, et al. Impaired glutamate uptake in the R6 Huntington's disease transgenic mice. Neurobiol Dis 2001; 8: 807-21
38. Guidetti P, Luthi-Carter RE, Augood SJ, Schwarcz R. Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease. Neurobiol Dis 2004; 17: 455-61.
39. Giorgini F, Guidetti P, Nguyen Q, Bennett SC, Muchowski PJ. A genomic screen in yeast implicates kynurenine 3-moneoxygenase as a therapeutic target for Huntington disease. Nat Genet 2005; 37: 526-31.
40. Chen N, Luo T, Wellington C, Metzler M, McCutcheon K, Hayden MR, et al. Subtype-specific enhancement of NMDA receptor currents by mutant huntingtin. J Neurochem 1999; 72: 1890-8.
41. Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 2002; 33: 849-60.
42. Li L, Fan M, Icton CD, Chen N, Leavitt BR, Hayden MR, et al. Role of NR2B-typc NMDA receptors in selective neurodegeneration in Huntington disease. Neurobiol Aging 2003; 24: 1113-21.
43. Fan MM, Fernandes HB, Zhang LY, Hayden MR, Raymond LA. Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntingtons disease. J Neurosci 2007;27: 3768-79.
44. Bezprozvanny I, Hayden MR. Deranged neuronal calcium signaling and Huntington disease. Biochem Biophys Res Commun 2004; 322:1310-7.
45. Jenkins BG, Rosas HD, Chen YC, Makabe T, Myers R, Mac-Donald M, et al. 1H NMR spectroscopy studies of Huntington's disease: Correlations with CAG repeat numbers. Neurology 1998; 50:1357-65.
46. Gu M, Gash, MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol 1996;39: 385-9.
47. Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Mugit MM, et al. Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997; 41: 646-53.
48. Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann Neurol 1999; 45: 25-32.
49. Benchoua A, Trioulier Y, Zala D, Gaillard MC, Lefort N, Dufour N, et al. Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated Huntingtin. Mol Biol Cell 2006; 17: 1652-63.
50. Sawa A, Wiegan GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr, et al. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med 1999; 5: 1194-8.
51. Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WT, et al. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci 2002; 5: 731-6.
52. Choo YS, Johnson GV, MacDonald M, Detloff PJ, Lesort M. Mutant Huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet 2004; 13: 1407-20.
53. Squitieri F, Cannella M, Sgarbi G, Maglione V, Falleni A, Lenzi P, et al. Severe ultrustructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 2006; 127:217-20.
54. Chang, DT, Rintoul GL, Pandipati S, Reynolds IJ. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 2006; 22: 388-400.
55. Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski U, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006; 4: 349-62.
56. Chao MV. Neurotrophins and their receptors: A convergence point for many signaling pathways. Nat Rev Neurosci 2003; 4: 299-309.
57. Zuccato C, Cattaneo E. Role of brain-derived neurotrophic factor in Huntington's disease. Prog Neurobiol 2007; 81: 294-30.
58. Baquet ZC, Bickford PC, Jones KR. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 2005; 25: 6251-9.
59. Strand AD, Baquet ZC, Aragaki AK, Holman P, Yang L, Cleren C, et al. Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci 2007; 27: 11758-68.
60. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of Huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001; 293: 493-98.
61. Borrell-Pagès M, Canals JM, Cordelières FP, Parker JA, Pineda JR, Grange G, et al. Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase. J Clin Invest 2006; 116: 1410-24.
62. Canals JM, Pineda JR, Torres-Peraza JF, Basch M, Martín-Ibañez R, Muñoz MT, et al. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci 2004; 24: 7727-39.
63. Gharami K, Xie Y, An JJ, Tonegawa S, Xu B. Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice. J Neurochem. 2008; 105: 369-79.
64. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled nouronall genes. Nat Genet 2003; 35; 76-83.
65. Dompierre JP, Godin JD. Charrin BC, Cordelières FP, King SJ, Humbert S, et al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci 2007; 27: 3571-83.
66. del Toro D, Canals JM, Gines S, Kojima M, Egea G, Alberch J. Mutant huntingtin impairs die post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism. J Neurosci 2006; 26:12748-57.
67. Mihm MJ, Amann DK Schanbacher BL, Altschuld RA, Bauer JA, Hoyt KR, et al. Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 2007; 25: 297-308.
68. Bolt JM, Lewis GP. Huntington's chorea. A study of liver function and histology. Q J Med 1973; 42: 151-74.
69. Forrest AD. Some observations on Huntington's chorea. J Ment Sci 1957; 103: 507-13.
70. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, et al. Trehalose alleviates polyglutamine-modiated pathology in a mouse model of Huntington disease. Nat Med 2004; 10: 148-54.
71. Chiang MC, Chen HM, Lee YH, Chang HH, Wu YC, Soong BW, et al. Dysregulation of C/EBPalpha by mutant Huntingtin causes the urea cycle deficiency in Huntington's disease. Hum Mol Genet 2007; 16:483-98.
72. Podolsky S, Leopold NA. Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease. Gerontology 1977; 23: 55-63
73. Farrer LA. Diabetes mellitus in Huntington disease. Clin Genet 1985; 27: 62-7.
74. Schubotz R, Hausmann L, Kaffarnik H, Zehner J, Oepen H. Fatty acid patterns and glucose tolerance in Huntington's chorea. Res Exp Med (Berl) 1976; 167: 203-15.
75. Bjorkqvist M, Fox M, Renström E, Wierup N, Petersén A, Gil J, et al. The R6/2 transgenic mouse Model of Huntington's disease develops diabetes due to deficient beta-cell mass and exocytosis. Hum Mol Genet 2005; 14: 565-74.
76. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP, et al. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA 2003; 100: 2911-6.
77. Chou SY, Lee YC, Chen HM, Chiang MC, Lai HL, Chang HH, et al. CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. J Neurochem 2005; 93: 310-20.
78. Cepeda C, Hurst RS, Calvert UK, Hernandez-Echeagaray E, Nguyen OK, Jocoy E, et al. Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease. J Neurosci 2003; 23: 961-69.
79. Varani K, Rigamonti D, Sipio, Camurri A, Borea PA, Cattabeni F, et al. Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin. FASEB J 2001; 15: 1245-7.
80. Cha JH, Frey AS, Alsdorf SA, Kerner JA, Kosinski CM, Mangiarini L, et al. Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Philos Trans R Soc Lond B Biol Sci 1999; 354: 981-9.
81. Glass M, Dragunow K Faull RL. The pattern of neurodegeneration in Huntington's disease: A comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 2000; 97: 505-19.
82. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, et al. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum Mol Genet 2000; 9: 1259-71
83. 2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J Biol Chem 2005; 280: 14331-40.
84. Sugars KL, Brown R, Cook LJ, Siwartz J, Rubinsztein DC. Decreased cAMP response element-mediated transcription: An early event in exon 1 and full-length cell models of Huntington's disease that contributes to polyglutamine pathogenesis. J Biol Chem 2004; 279:4988-99.
85. 2A receptor signaling in a mouse model of Huntington disease. Neurobiol Dis 2006; 23: 44-53.
86. Sastre M, Garcia-Sevilla JA. Density of alpha-2A adrenoceptors and Gi proteins in the human brain: Ratio of high-affinity agonist sites to antagonist sites and effect of age. J Pharmacol Exp Ther 1994; 269: 1062-72.
87. Kenakin T. Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry. Trends Pharmacol Sci 1997; 18:456-64.
88. Morton AJ, Leavens W. Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res Bull 2000; 52: 51-9.
89. Spektor BS, Miller DW, Hollingsworth ZR, Kaneko YA, Solano SM, Johnson JK, et al. Differential D1 and D2 receptor-mediated effects on immediate early gene induction in a transgenic mouse model of Huntington's disease. Brain Res Mol Brain Res 2002; 102:118-28.
90. Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci USA 1998; 95: 6480-5.
91. Klapstein GJ, Fisher RS, Zanjani H, Cepeda C, Jokel ES, Chesselet MF, et al. Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice. J Neurophysiol 2001; 86: 2667-77.
92. 2A receptor agonist CGS21680 in the striatum of Huntington's disease versus wild-type mice. Neurosci Lett 2007; 417: 78-83.
93. 2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington's disease patients with predominant chorea. Neurosci Lett 2006; 393: 27-30.
94. 2A receptor function in peripheral blood cells in Huntington's disease. FASEB J 2003; 17: 2148-50.
95. Varani Y, Bachoud-Lévi AC, Mariotti C, Tarditi A, Abbracchio MP, Gasperi V, et al. Biological abnormalities of peripheral A(2A) receptors in a large representation of polyglutamine disorders and Huntington's disease stages. Neurobiol Dis 2007; 27: 36-43.
96. Ferré S, O'Connor WT, Fuxe K, Ungerstedt U. The striopallidal neuron: A main locus for adenosine-dopamine interactions in the brain. J Neurosci 1993; 13; 5402-6.
97. 2:A adenosine receptor gene expression in developing rat brain. Brain Res Mol Brain Res 1993; 20: 313-27.
98. Lee M, Hwang JT, Lee HJ, Jung SN, Yang I, Chi SG, et al. AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 transcriptional activity and its target gene expression under hypoxic conditions in DU145 cells. J Biol Chem 2003; 278: 39653-61.
99. 2A receptors in regulating GABAergic synaptic transmission in striata1 medium spiny neurons. J Neurosci 1996; 16: 605-11.
100. 2A receptor in the rat striatum. J Neurochem 1997; 69: 315-21.
101. 2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuoprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 2002; 22: 1967-75
102. 2A antagonists. J Neurosci 2003; 23: 5361-9.
103. 2A adenosine receptor antagonism differentially modifies striatal glutamate outflow in vivo in young and aged rats. Neuroreport 2000; 11: 2591-5.
104. Ferré S, Agnati LF, Ciruela F, Lluis C, Woods AS, Fuxe K, et al. Neurotransmitter receptor heteromers and their integrative role in 'local modules': The striatal spine module. Brain Res Rev 2007; 55: 55-67.
105. 2A receptor heteromers. J Neurosci 2006; 26: 2080-7.
106. 2A receptors and dopamine D2 receptors. J Biol Chem 2002; 277: 18091-7.
107. 2A and glutamate mGlu5 receptors: Implications for striatal neuronal function. Proc Natl Acad Sci USA 2002; 99: 11940-5
108. Chiang MC, Juo CG, Chang HH, Chen HM, Yi EC, Chem Y. Systematic uncovering of multiple pathways underlying the pathology of Huntington disease by an acid-cleavable isotope-coded affinity tag approach. Mol Cell Proteomics 2007; 6: 781-97.
109. Morton A. Huntington's disease and combination drug therapy. Gene Expression Omnibus 2003.
110. 2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 2007; 32: 2249-59.
111. Ferré S, Borycz J, Goldberg SR, Hope BT, Morales M, Lluis C, et al. Role of adenosine in the control of homosynaptic plasticity in striatal excitatory synapses. J Integr Neurosci 2005; 4: 445-64.
112. Ferré S, Fredholm BB, Morelli M, Popoli P, Fuxe K. Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 1997; 20: 482-7.
113. 2A receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 1995; 287: 215-7.
114. 2A adenosine receptors differentially regulate spontaneous and K+-evoked glutamate release in vivo in young and aged rats. Neuroreport 1999; 10: 687-91.
115. Pintor A, Quarta D, Pèzzola A, Reggio R, Popoli P. SCH 58261 (an adenosine A(2A) receptor antagonist) reduces, only at low doses, K(+)-evoked glutamate release in the striatum. Eur J Pharmacol 2001; 421: 177-80.
116. 2 receptor antagonist, reduces cerebral ischemic injury in the mongolian gerbil. Life Sci 1994; 55: PL61-5.
117. 2A receptors results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport 1998; 9: 3955-9.
118. 2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. J Neurosci 1999; 19: 9192-200.
119. 2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices. Neuropharmacol 2003; 45: 201-10.
120. 2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behaviour and ischemic brain damage induced by permanent focal ischemia in the rat. Brain Res 2003; 959: 243-50.
121. Orlando LR, Alsdorf SA, Penney JB Jr, Young AB. The role of Group I and group II metabotropic glutamate receptors in modulation of striatal NMDA and quinolinic acid toxicity. Exp Neurol 2001; 167: 196-204.
122. Schulz PE, Cook EP, Johnston D. Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation. J Neurosci 1994; 14: 5325-37.
123. 2A receptor blockade diferentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum. J Neurosci Res 2004; 77: 100-7.
124. Danbolt NC. Glutamate uptake. Prog Neurobiol 2001; 65: 1-105.
125. 2A adenosine receptors. J Pharmacol Sci 2004; 94: 100-2.
126. 2A adenosine receptors. Glia 2002; 39: 133-47.
127. 2A adenosine receptors. Life Sci 2001; 68: 1343-50.
128. 2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors. J Neurochem 2004; 89: 152-6.
129. Levine MS, Klapstein GJ, Koppel A, Gruen E, Cepeda C, Vargas ME, et al. Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J Neurosci Res 1999; 58: 515-32.
130. Cepeda C, Ariano MA, Calvert CR, Flores-Hernández J, Chandler SH, Leavitt BR, et al. NMDA receptor function in mouse models of Huntington disease. J Neurosci Res 2001; 66: 525-39.
131. Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, et al. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J Neurosci 2001; 21: 9112-23.
132. 2A receptor antagonists as neuroprotective agents. Curr Med Chem CNS Agents 2004; 4: 35-45.
133. 2A receptor antagonistm and neuroprotection: mechanisms, lights and shadows. Crit Rev Neurobiol 2004; 16: 99- 06.
134. Norenberg W, Wirkner, Illes P. Effect of adenosine and some of its structural analogues on the conductance of NMDA receptor channels in a subset of rat neostriatal neurones. Br J Pharmacol 1997; 122: 71-80
135. Wirkner K, Assmann H, Köles L, Gerevich Z, Franke H, Nörenberg W, et al. Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. Br J Pharmacol 2000; 130: 259-69.
136. Robledo P, Ursu G, Mahy N. Effects of adenosine and gamma-aminobutyric acid A receptor antagonists on N-methyl-D-aspartate induced neurotoxicity in the rat hippocampus. Hippocampus 1999; 9: 527-33.
137. Beal MF, Ferrante RJ. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci 2004; 5: 373-84.
138. 2A receptor attenuates 3-nitropropionic acid-induced striatal damage. J Neurochem 2004; 88: 538-44.
139. Alfinito PD, Wang SP, Manzino L, Rijhsinghani S, Zeevalk GD, Sonsalla PK. Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively. J Neurosci 2003; 23: 10982-7.
140. Blum D, Hourez R, Galas MC, Popoli P, Schiffmann SN. Adenosine receptors and Huntington's disease: Implications for pathogenesis and therapeutics. Lancet Neurol 2003; 2: 366-74.
141. Bantubungi K, Jacquard C, Greco A, Pintor A, Chtarto A, Tai K, et al. Minocycline in phenotypic models of Huntingtons disease. Neurobiol Dis 2005; 18: 206-17.
142. 2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-type-selective in-activation. J Neurosci 2006; 26: 1137-8.
143. Yu L, Huang Z, Mariani J, Wang Y, Moskowitz M, Chen JF. Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat Med 2004; 10: 1081-7.
144. Lee FS, Chao MV. Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 2001; 98: 3555-60.
145. Wiese S, Jablonka S, Holtmann B, Orel N, Rajagopal R, Chao MV, et al. Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB. Proc Natl Acad Sci USA 2007; 104: 17210-5.
146. Mojsilovic-Petrovic J, Jeong GB, Crocker A, Arneja A, David S, Russell DS, et al. Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors. J Neurosci 2006; 26: 9250-63.
147. 2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices. J Neurosci 2004; 24: 2905-13.
148. Pousinha PA, Diogenes JM, Ribeiro AJ, Sebastiao AM. Triggering of BDNF ficilitatory action on neuromuscular transmission by adenosine A(2A) receptors. Neurosci 2006; 404:143-7.
149. Tebano MT. Martire A, Potenza RL, Grò C, Pepponi R, Armida M, et al. Adenosinc A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus. J Neurochem 2008; 104: 279-86.
150. Cyr K Sotnikova TD, Gainetdinov RR, Caron MG Dopamine enhances motor and neurapathological consequences of polyglutamine expanded huntingtin. FASEB J 2006; 20: 2541-3.
151. Charvin D, Vanhoutte P, Pages C, Borrelli E, Caboche J; Unraveling a role for dopamine in Huntingon's disease: The dual role of reactive-oxygen species and D2 receptor stimulation. Proc Natl Acad Sci USA 2005; 102: 12218-23.
152. Charvin D, Roze E, Perrin V, Deyts C, Betuing S, Pags̀ C, et al. Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo. Neurobiol Dis 2008; 29: 22-9.
153. Tang TS, Chen X, Liu J, Bezprozvanny I. Dopaminergic signaling and striatal neurodegeneration in Huntington's disease. J Neurosci 2007; 27: 7899-910.
154. Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF. Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiol Behav 2007; 92: 210-7.
155. Gong B, Lim MC, Wanderer J, Wyttenbach A, Morton AJ. Time-lapse analysis of aggregate formation in an inducible PC12 cell model of Huntington's disease reveals time-dependent aggregate formation that transiently delays cell death. Brain Res Bull 2008; 75: 146-57.
156. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004; 431: 805-10.
157. Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 2007; 130: 1759-66.
158. Simmons DA, Casale M, Alcon B, Pham N, Narayan N, Lynch G. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia 2007; 55: 1074-84.
159. 2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia 2003; 43: 190-4.
160. 2A receptor stimulation potentiates nitric oxide release by activated microglia. J Neurochem 2005; 95: 919-29.
161. Fiebich BL, Biber K, Lieb K, van Calker D, Berger M, Bauer J, et al. Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Glia 1996; 18: 152-60.
162. 2A receptor antagonist SCH 58621 on cyclooxygenase-2 expression, glial activation and brain-derived neurotrophic factor availability in a rat model of striatal neurodegeneration. J Neuropathol Exp Neurol 2007; 66: 363-71.
163. Dionisotti S, Ferrara S, Molta C, Zocchi C, Ongini E. Labeling of A2A adenosine receptors in human platelets by use of the new nonxanthine antagonist radioligand [3H]SCH 58261. J Pharmacol Exp Ther 1996; 278: 1209-14.
164. Nekooeian AA, Tabrizchi R. Haemodynamic effects of a selective adenosine A2A receptor agonist, CGS 21680, in chronic heart failure in anaesthetized rats. Br J Pharmacol 1998; 125: 651-8.
165. Lozza G, Conti A, Ongini E, Monopoli A. Cardioprotective effects of adenosine A1 and A2A receptor agonists in the isolated rat heart. Pharmacol Res 1997; 35: 57-64.
166. Carini R, Grazia De Cesaris M, Splendore R, Baldanzi G, Nitti MP, Alchera E, et al. Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning. Gastroenterology 2004; 127: 914-23.
167. Day YJ, Li Y, Rieger JM, Ramos SI, Okusa MD, Linden J. A2A adenosine receptors on bone marrow-derived cells protect liver from ischemia-reperfusion injury. J Immunol 2005; 174: 5040-6.
168. Day YJ, Huang L, McDuffie MJ, Rosin DL, Ye H, Chen JF, et al. Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells. J Clin Invest 2003; 112: 883-91.
169. Day YJ, Huang L, Ye H, Linden J,Okusa MD. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: Role of macrophages. Am J Physiol Renal Physiol 2005; 288: F722-31.
170. Capecchi PL, Camurri A, Pompella G, Mazzola A, Maccherini M, Diciolla F, et al. Upregulation of A2A adenosine receptor expression by TNF-alpha in PBMC of patients with CHF: A regulatory mechanism of inflammation. J Card Fail 2005; 11: 67-73.
171. Bshesh K, Zhao B, Spight D, Biaggioni I, Feokistov I, Denenberg A, et al. The A2A receptor mediates an endogenous regulatory pathway of cytokine expression in THP-1 cells. J Leukoc Biol 2002; 72: 1027-36
172. Yang Z, Day YJ, Toufektsian MC, Ramos SI, Marshall M, Wang XQ, et al. Infarct-sparing effect of A2A-adenosine receptor activation is due primarily to its action on lymphocytes. Circulation 2005; 111: 2190-7.
173. Harada N, Okajima K, Murakami K, Usune S, Sato C, Ohshima K, et al. Adenosine and selective A(2A) receptor agonists reduce ischemia/ reperfusion injury of rat liver mainly by inhibiting leukocyte activation. J Pharmacol Exp Ther 2000; 294: 1034-42.
174. Gianfriddo M, Corsi C, Melani A, Pèzzola A, Reggio R, Popoli P, et al. Adenosine A(2A) antagonism increases striatal glutamate outflow in the quinolinic acid rat model of Huntington's disease. Brain Res 2003; 979: 225-9.
175. Impagnatiello F, Bastia E, Ongini E, Monopoli A. Adenosine receptors in neurological disorders. Emerg Ther Targets 2000; 4: 635-64.
176. Karcz-Kubicha M, Antoniou K, Terasmaa A, Quarta D, Solinas M, Justinova Z, et al. Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic Administration. Neuropsychopharmacology 2003; 28: 1281-91.
177. Domenici MR, Scattoni ML, Martire A, Lastoria, G, Potenza RL, Borioni A, et al. Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6/2 Huntington's disease mice. Neurobiol Dis 2007; 28: 197-205.
178. Scattoni ML, Valanzano A, Pezzola A, March ZD, Fusco FR, Popoli P, et al. Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease. Behav Brain Res 2007; 176: 216-21
179. Gianfriddo M, Melani A, Turchi D, Giovannini MG, Pedata F. Adenosine and glutamate extracellular concentrations and mitogen-activated protein kinases in the striatum of Huntington transgenic mice. Selective antagonism of adenosine A2A receptors reduces transmitter outflow. Neurobiol Dis 2004; 17: 77-88.
180. 2A receptor antagonist istradefylline (KW-6002) is neuroprotective in a chronic brain slice explant model and improves performance in the R6/2 mouse model of Huntington disease. Annual Meeting Society for Neuroscience 2007, San Diego, California, Program # 798.13, Poster #P11.
181. 2A adenosine receptors in rescuing the nerve growth factor-induced neurite outgrowth impaired by blockage of the MAPK cascade. J Biol Chem 2002; 277: 33930-42.
182. 2A adenosine receptor via a novel interacting protein, Translin-associated protein X. Mol Pharmacol 2006; 70: 454-66.
183. 2A receptor agonists and antagonists. Neuroscience 1998; 85: 229-37.
184. Taylor JP, Tanaka F, Robitschek J, Sandoval CM, Taye A, Markovic-Plese S, et al. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum Mol Genet 2003; 12: 749-57.
185. Li SH, Lam S, Cheng AL, Li XJ. Intranuclear huntingtin increases the expression of caspase-1 and induces apaptosis. Hum Mol Genet 2000; 9: 2859-67.
186. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000; 6: 797-801.
187. Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ. Chung WM, et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 1999; 399: 263-7.
188. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 2004; 36: 585-95.
189. Williams A, Jahreiss L, Sarkar S, Saiki S, Menzies FM, Ravikumar B, et al. Aggregate-prone proteins are cleared from the cytosol by autophagy: Therapeutic implications. Curr Top Dev Biol 2006; 76: 89-101.
190. Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell? Annu Rev Biochem 1998; 67: 821-55.
191. Kuramoto N, Wilkins ME, Fairfax BP, Revilla-Sanchez R, Terunuma M, Tamaki K, et al. Phospho-dependent functional modulation of GABA(B) receptors by the metabolic sensor AMP-dependent protein kinase. Neuron 2007; 53: 233-47.
192. Tsuboi T, da Silva Xavier G, Leclerc I. Rutter GA. 5′-AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics. J Biol Chem 2003; 278: 52042-51.
193. Hong YH, Varanasi US, Yang W, Leff T. AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem 2003; 278: 27495-501.
194. Kim SJ, Nian C, Widenmaier S, McIntosh CH. Glucose-dependent insulinotropic polypeptide (GIP) mediated up-regulation of {beta}-cell anti-apoptotic Bcl-2 genc expression is coordinated by cAMP-response element binding protein (CREB) and cAMP-responsive CREB coactivator 2 (TORC2). Mol Cell Biol 2008; 28: 1644-56.
195. Hurley RL, Barré LK, Wood SD, Anderson KA, Kemp BE, Means AR, et al. Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J Biol Chem 2006; 281: 36662-72.
196. Halldner L, Lopes LV, Daré E, Lindström K, Johansson B, Ledent C, et al. Binding of adenosine receptor ligands to brain of adenosine receptor knock-out mice: Evidence that CGS 21680 binds to A1 receptors in hippocampus. Naunyn Schmiedebergs Arch Pharmacol 2004; 370: 270-8.