Mitochondrial-associated metabolic changes and neurodegeneration in Huntington's disease - from clinical features to the bench

Current Drug Targets

Volumn 11, Issue 10, 2010, Pages 1218-1236

  Rosenstock, Tatiana R ^a   Duarte, Ana I ^a   Rego, A Cristina ^a,b  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Calcium handling; Excitotoxicity; Huntingtin; Mitochondrial dysfunction; Mitochondrial fission and fusion; Neurodegeneration; Transcription deregulation

Indexed keywords

CALCIUM; GLUCOSE; GLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

APOPTOSIS; ARTICLE; BODY WEIGHT; CALCIUM CELL LEVEL; CELL DEATH; CLINICAL FEATURE; ENDOCRINE DISEASE; EXCITOTOXICITY; GLUCOSE METABOLISM; HUMAN; HUNTINGTON CHOREA; METABOLIC DISORDER; METABOLIC PARAMETERS; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL PERMEABILITY; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; OXIDATIVE STRESS; TRANSCRIPTION REGULATION;

EID: 77957993152     PISSN: 13894501     EISSN: None     Source Type: Journal    
DOI: 10.2174/1389450111007011218     Document Type: Article

References (258)

1. Vonsattel JP, DiFiglia M. Huntington disease. J Neuropathol Exp Neurol 1998; 57: 369-84.
2. Ho LW, Carmichael J, Swart J, et al. The molecular biology of Huntington's disease. Psychol Med 2001; 31: 3-14.
3. Warby SC, Graham RK, Hayden MR. Huntington's disease. In: Pagon RA, Bird TC, Dolan CR, Stephens K, Eds. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-1998 Oct 23 [updated 2005 Aug 30].
4. Harper PS. In: Huntington's Disease. London: Saunders 2001; pp 53-7.
5. Imarisio S, Carmichael J, Korolchuk V, et al. Huntington's disease: from pathology and genetics to potential therapies. Biochem J 2008; 412: 191-209.
6. 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.
7. Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington's disease. Nat Rev Neurosci 2005; 6: 919-30.
8. Gil JM, Rego AC. Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 2008; 28(10): 2156.
9. Arning L, Kraus PH, Valentin S, et al. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease. Neurogenetics 2005; 6: 25-8.
10. Wexler NS, Lorimer J, Porter J, et al. U.S.-Venezuela Collaborative Research Project. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci USA 2004; 101: 3498-503.
11. Mitchell IJ, Cooper AJ, Griffiths MR. The selective vulnerability of [34] Gil JM, Rego AC. The R6 lines of transgenic mice: a model for striatopallidal neurons. Prog Neurobiol 1999; 59: 691-719.
12. Biglan KM, Ross CA, Langbehn DR, et al. PREDICT-HD Investigators of the Huntington Study Group. Motor abnormalities in premanifest persons with Huntington's disease: the PREDICT- HD study. Mov Disord 2009; 24: 1763-72.
13. Montoya A, Price BH, Menear M, Lepage M. Brain imaging and cognitive dysfunctions in Huntington's disease. J Psychiatry Neurosci 2006; 31: 21-9.
14. Rosas HD, Liu AK, Hersch S, et al. Regional and progressive thinning of the cortical ribbon in Huntington's disease. Neurology 2002; 58: 695-701.
15. Rosas HD, Hevelone ND, Zaleta AK, et al. Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 2005; 65: 745-7.
16. Kremer HP, Roos RA, Dingjan G, Marani E, Bots GT. Atrophy of the hypothalamic lateral tuberal nucleus in Huntington's disease. J Neuropathol Exp Neurol 1990; 49: 371-82.
17. Kremer HP, Roos RA, Dingjan GM, et al. The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington's disease. Neurosci Lett 1991; 132: 101-04.
18. Petersén A, Gil J, Maat-Schieman ML, et al. Orexin loss in Huntington's disease. Hum Mol Genet 2005; 14: 39-47.
19. Aziz A, Fronczek R, Maat-Schieman M, et al. Hypocretin and melanin-concentrating hormone in patients with Huntington disease. Brain Pathol 2008; 18: 474-83.
20. Kassubek J, Juengling FD, Kioschies T, et al. Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study. J Neurol Neurosurg Psychiatry 2004; 75: 213-20.
21. Douaud G, Gaura V, Ribeiro MJ, et al. Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study. Neuroimage 2006; 32: 1562-75.
22. Sawiak SJ, Wood NI, Williams GB, Morton AJ, Carpenter TA. Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry. Neurobiol Dis 2009; 33: 20-7.
23. DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997; 277: 1990-3.
24. Kuemmerle S, Gutekunst CA, Klein AM, et al. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann Neurol 1999; 46: 842-9.
25. Becher MW, Kotzuk JA, Sharp AH, et al. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol Dis 1998; 4: 387-97.
26. DiFiglia M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci 1990; 13: 286-9.
27. Goldenthal MJ, Marin-Garcia J. Mitochondrial signaling pathways: a receiver/integrator organelle. Mol Cell Biochem 2004; 262: 1-16.
28. Scarpulla RC. Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 2006; 97: 673-83.
29. Storey E, Kowall NW, Finn SF, Mazurek MF, Beal MF. The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. Ann Neurol 1992; 32: 526-4.
30. Arzberger T, Krampfl K, Leimgruber S, Weindl A. Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington's disease-an in situ hybridization study. J Neuropathol Exp Neurol 1997; 56: 440-54.
31. Lievens JC, Woodman B, Mahal A, et al. Impaired glutamate uptake in the R6 Huntington's disease transgenic mice. Neurobiol Dis 2001; 8: 807-21.
32. Shin JY, Fang ZH, Yu ZX, et al. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005; 171: 1001-12.
33. Mangiarini L, Sathasivam K, Seller M, et al. 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. screening new therapies for Huntington's disease. Brain Res Rev 2009; 59(2): 410-31.
34. Beal MF, Kowall NW, Ellison DW, et al. Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 1986; 321(6066): 168-71.
35. Beal MF, Ferrante RJ, Swartz KJ, Kowall NW. Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. J Neurosci 1991; 11: 1649-59.
36. Ferrante RJ, Kowall NW, Cipolloni PB, Storey E, Beal MF. Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. Exp Neurol 1993; 119(1): 46-71.
37. Dessi F, Ben-Ari Y, Charriaut-Marlangue C. Ruthenium red protects against glutamate-induced neuronal death in cerebellar culture. Neurosci Lett 1995; 201(1): 53-6.
38. Slow EJ, van Raamsdonk J, Rogers D, et al. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 2003; 12: 1555-67.
39. Wheeler VC, White JK, Gutenkunst CA, et al. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum Mol Genet 2000; 9: 503-13.
40. Panov AV, Gutekunst CA, Leavitt BR, et al. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci 2002; 5: 731-6.
41. Oliveira JM, Chen S, Almeida S, et al. Mitochondrial-dependent Ca2+ handling in Huntington's disease striatal cells: effect of histone deacetylase inhibitors. J Neurosci 2006; 26: 11174-86.
42. Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev 2006; 86: 369-408.
43. Young AB, Greenamyre JT, Hollingsworth Z, et al. NMDA receptor losses in putamen from patients with Huntington's disease. Science 1988; 241: 981-3.
44. Albin RL, Young AB, Penney JB, et al. Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington's disease. N Engl J Med 1990; 322: 1293-8.
45. Luthi-Carter R, Apostol BL, Dunah AW, et al. Complex alteration of NMDA receptors in transgenic Huntington's disease mouse brain: analysis of mRNA and protein expression, plasma membrane association, interacting proteins, and phosphorylation. Neurobiol Dis 2003; 14: 624-36.
46. Cha JHJ, Kosinski CM, Kerner JA, 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.
47. Luthi-Carter R, Strand A, Peters NL, et al. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum Mol Genet 2000; 9: 1259-71.
48. Ali NJ, Levine MS. Changes in expression of N-methyl-D- aspartate receptor subunits occur early in the R6/2 mouse model of Huntington's disease. Dev Neurosci 2006; 28: 230-8.
49. Li L, Fan M, Icton CD, et al. Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease. Neurobiol Aging 2003; 24: 1113-21.
50. Jarabek BR, Yasuda RP, Wolfe BB. Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a huntington's mouse model. Brain 2004; 127: 505-16.
51. Schilling G, Becher MW, Sharp AH, et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N- terminal fragment of huntingtin. Hum Mol Genet 1999; 8: 397-407.
52. Yu Z-X, Li S-H, Evans J, et al. Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J Neurosci 2003; 23: 2193-202.
53. 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.
54. Fan J, Cowan CM, Zhang LY, Hayden MR, Raymond LA. Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease. J Neurosci 2009; 29(35): 10928-38.
55. Zeron MM, Chen N, Moshaver A, et al. Mutant huntingtin enhances excitotoxic cell death. Mol Cell Neurosci 2001; 17: 41-53.
56. Zeron MM, Hansson O, Chen N, 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.
57. Song C, Zhang Y, Parsons CG, Liu YF. Expression of polyglutamine expanded huntingtin induces tyrosine phosphorylation of N-methyl-D aspartate receptors. J Biol Chem 2003; 278: 33364-9.
58. Tang TS, Slow E, Lupu V, et al. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc Natl Acad Sci USA 2005; 102: 2602-7.
59. Zhang W, Vazquez L, Apperson M, Kennedy MB. Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus. J Neurosci 1999; 19: 96-108.
60. Hansson O, Petersén A, Leist M, et al. Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. Proc Natl Acad Sci USA 1999; 96(15): 8727-32.
61. Hansson O, Castilho RF, Korhonen L, et al. Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length. J Neurochem 2001; 78(4): 694-703.
62. Hansson O, Guatteo E, Mercuri NB, et al. Resistance to NMDA toxicity correlates with appearance of nuclear inclusions, behavioural deficits and changes in calcium homeostasis in mice transgenic for exon 1 of the huntington gene. Eur J Neurosci 2001; 14(9): 1492-504.
63. Graham RK, Pouladi MA, Joshi P, et al. Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease. J Neurosci 2009; 29(7): 2193-204.
64. Joshi PR, Wu NP, André VM, et al. Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington disease. J Neurosci 2009; 29(8): 2414-27.
65. Ferrante RJ, Andreassen OA, Dedeoglu A, et al. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci 2002; 22: 1592-9.
66. Schiefer J, Landwehrmeyer GB, Lüesse HG, et al. Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington's disease. Mov Disord 2002; 17: 748-57.
67. Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996; 47: S233-41.
68. Wu J, Li Q, Bezprozvanny I. Evaluation of Dimebon in cellularmodel of Huntington's disease. Mol Neurodegener 2008; 3: 15.
69. Okamoto S, Pouladi MA, Talantova M, et al. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med 2009; 15(12):1407-13.
70. Milnerwood AJ, Gladding CM, Pouladi MA, et al. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Neuron 2010; 65(2): 178-90.
71. Baysal K, Jung KK, Gunter KK, Gunter TE, Brierley GP. Na - dependent Ca+2 efflux mechanism of heart mitochondria is not a passive Ca+2/ 2Na+ exchanger. Am J Physiol 1994; 266: C800-5.
72. Hunter DR, Haworth RA. The Ca+2-induced membrane transition in mitochondria. The protective mechanisms. Arch Biochem Biophys 1979; 195: 453-9.
73. Hajnóczky G, Csordás G, Das S, et al. Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. Cell Calcium 2006; 40: 553-60.
74. Desplats PA, Kass KE, Gilmartin T, et al. Selective deficits in the expression of striatal-enriched mRNAs in Huntington's disease. J Neurochem 2006; 3: 743-57.
75. Nicholls DG, Budd SL. Mitochondrial and neuronal survival. Physiol Rev 2000; 80: 315-60.
76. Robb-Gaspers LD, Rutter GA, Burnett P, et al. Coupling between cytosolic and mitochondrial calcium oscillations: role in the regulation of hepatic metabolism. Biochim Biophys Acta 1998; 1366: 17-32.
77. Gutekunst CA, Li SH, Yi H, et al. The cellular and subcellular localization of huntingtin-associated protein 1 (HAP1): comparison with huntingtin in rat and human. J Neurosci 1998; 18: 7674-86.
78. Sawa A, Wiegand GW, Cooper J, et al. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med 1999; 5: 1194-8.
79. Petrasch-Parwez E, Nguyen HP, Löbbecke-Schumacher M, et al. Cellular and subcellular localization of Huntingtin [corrected] aggregates in the brain of a rat transgenic for Huntington disease. J Comp Neurol 2007; 501: 716-30.
80. Mihm MJ, Amann DM, Schanbacher BL, et al. Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 2007; 25: 297-308.
81. Panov AV, Burke JR, Strittmatter WJ, Greenamyre JT. In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: relevance to Huntington's disease. Arch Biochem Biophys 2003; 410: 1-6.
82. Rizzuto R, Pinton P, Carrington W, et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca+2 responses. Science 1998; 280: 1763-6.
83. Tang TS, Tu H, Chan EY, et al. Huntingtin and huntingtin associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 2003; 39: 227-39.
84. Tang TS, Guo C, Wang H, Chen X, Bezprozvanny I. Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C- terminal fragment in a Huntington's disease mouse model. J Neurosci 2009; 29: 1257-66.
85. Milakovic T, Quintanilla RA, Johnson GV. Mutant huntingtin expression induces mitochondrial calcium handling defects in clonal striatal cells: functional consequences. J Biol Chem 2006; 281(46): 34785-95.
86. Puranam KL, Wu G, Strittmatter WJ, Burke JR. Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria. Biochem Biophys Res Commun 2006; 341: 607-13.
87. Perluigi M, Poon HF, Maragos W, et al. Proteomic analysis of protein expression and oxidative modification in R6/2 transgenic mice: a model of Huntington disease. Mol Cell Proteom 2005; 4: 1849-61.
88. Tabrizi SJ, Workman J, Hart PE, et al. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol 2000; 47: 80-6.
89. Pérez-Severiano F, Escalante B, Vergara P, Ríos 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.
90. Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad Sci 2008; 1147: 358-82.
91. van Roon-Mom WM, Pepers BA, 't Hoen PA, et al. Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease. BMC Mol Biol 2008; 9: 84.
92. Calkins MJ, Jakel RJ, Johnson DA, et al. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2- mediated transcription. Proc Natl Acad Sci USA 2005; 102: 244-9.
93. Smith KM, Matson S, Matson WR, et al. Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice. Biochim Biophys Acta 2006; 1762: 616-26.
94. Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis 2001; 8: 479-91.
95. Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci 2000; 20: 4389-97.
96. Schilling G, Coonfield ML, Ross CA, Borchelt DR. Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model. Neurosci Lett 2001; 315: 149-53.
97. Stack EC, Smith KM, Ryu H, et al. Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice. Biochim Biophys Acta 2006; 1762: 373-80.
98. Dedeoglu A, Kubilus JK, Yang L, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem 2003; 85: 1359-67.
99. Matthews RT, Yang LJenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J Neurosci 1998; 18: 156-63.
100. Shear DA, Haik KL, Dunbar GL. Creatine reduces 3- nitropropionic-acid-induced cognitive and motor abnormalities in rats. Neuroreport 2000; 11: 1833-7.
101. Browne SE, Bowling AC, Macgarvey U, et al. Oxidative damage andmetabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997; 41: 646-53.
102. Dragunow M, Faull RL, Lawlor P, et al. In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes. Neuroreport 1995; 6: 1053-7.
103. Polidori MC, Mecocci P, Browne SE, et al. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex. Neurosci Lett 1999; 272: 53-6.
104. Clifford JJ, Drago J, Natoli AL, et al. Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease. Neuroscience 2002; 109: 81-8.
105. Rebec GV, Barton SJ, Ennis MD. Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington's disease gene. J Neurosci 2002; 22: RC202.
106. Rebec GV, Barton SJ, Marseilles AM, Collins K. Ascorbate treatment attenuates the Huntington behavioral phenotype in mice. Neuroreport 2003; 14: 1263-5.
107. Rosenstock TR, Carvalho ACP, Jurkiewicz A, et al. Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid. J Neurochem 2004; 88: 1220-8.
108. Yang CR, Yu RK. Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington's disease. J Neurosci Res 2009; 87: 26-33.
109. Ranen NG, Peyser CE, Coyle JT, et al. A controlled trial of idebenone in Huntington's disease. Mov Disord 1996; 11(5): 549-54.
110. Stack EC, Matson WR, Ferrante RJ. Evidence of oxidant damage in Huntington's disease: translational strategies using antioxidants. Ann NY Acad Sci 2008; 1147: 79-92.
111. Jakel RJ, Maragos WF. Neuronal cell death in Huntington's disease: a potential role for dopamine. Trends Neurosci 2000; 23: 239-45.
112. Cyr M, Sotnikova TD, Gainetdinov RR, Caron MG. Dopamine enhances motor and neuropathological consequences of polyglutamine expanded huntingtin. FASEB J 2006; 20: 2541-3.
113. Petersén Å, Larsen KE, Behr GG, et al. Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration. Human Molecular Genetics 2001; 10: 1243-54.
114. Benchoua A, Trioulier Y, Diguet E, et al. Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II. Hum Mol Genet 2008; 17: 1446-56.
115. Charvin D, Vanhoutte P, Page's C, et al. Unraveling a role for dopamine in Huntington's disease: the dual role of reactive oxygen species and D2 receptor stimulation. Proc Natl Acad Sci USA 2005; 102: 12218-23.
116. Paoletti P, Vila I, Rifé M, et al. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J Neurosci 2008; 28: 10090-101.
117. Tang TS, Chen X, Liu J, Bezprozvanny I. Dopaminergic signaling and striatal neurodegeneration in Huntington's disease. J Neurosci 2007; 27: 7899-910.
118. Petersén A, Hansson O, Puschban Z, et al. Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6- hydroxydopamine. Eur J Neurosci 2001; 14: 1425-35.
119. Brustovetsky N, Dubinsky JM. Dual responses of CNS mitochondria to elevated calcium. J Neurosci 2000; 20: 103-13.
120. Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J 1999; 341: 233-49.
121. Dubinsky JM, Levi Y. Calcium-induced activation of the mitochondrial permeability transition in hippocampal neurons. J Neurosci Res 1998; 53: 728-41.
122. 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.
123. Lim D, Fedrizzi L, Tartari M, et al. Calcium homeostasis and mitochondrial dysfunction in striatal neurons of Huntington disease. J Biol Chem 2008; 283: 5780-9.
124. Brustovetsky N, LaFrance R, Purl KJ, et al. Age-dependent changes in the calcium sensitivity of striatal mitochondria in mouse models of Huntington's Disease. J Neurochem 2005; 93: 1361-1370.
125. Oliveira JM, Jekabsons MB, Chen S, et al. Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J Neurochem 2007; 101: 241-9.
126. Sanchez I, Xu CJ, Juo P, et al. Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 1999; 22: 623-33.
127. Kiechle T, Dedeoglu A, Kubilus J, et al. Cytochrome C and caspase-9 expression in Huntington's disease. Neuromol Med 2002; 1: 183-95.
128. Ona VO, Li M, Vonsattel JP, et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 1999; 399: 263-7.
129. Vis JC, Schipper E, de Boer-van Huizen RT, et al. Expression pattern of apoptosis-related markers in Huntington's disease. Acta Neuropathol 2005; 109: 321-8.
130. Ferrer I, Blanco R, Cutillas B, Ambrosio S. Fas and Fas-L expression in Huntington's disease and Parkinson's disease. Neuropathol Appl Neurobiol 2000; 26: 424-33.
131. Wellington CL, Ellerby LM, Hackam AS, et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem 1998; 273(15): 9158-67.
132. Rigamonti D, Bauer JH, De-Fraja C, et al. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 2000; 20(10): 3705-13.
133. Rigamonti D, Sipione S, Goffredo D, et al. Huntingtin's neuroprotective activity occurs via inhibition of procaspase-9 processing. J Biol Chem 2001; 276(18): 14545-8.
134. Zhang X-D, Wang Y, Wang Y, et al. p53 mediates mitochondria dysfunction-triggered autophagy activation and cell death in rat striatum. Autophagy 2009; 5(3): 339-50.
135. Bizat N, Hermel JM, Boyer F, et al. Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3- nitropropionate: implications for Huntington's disease. J Neurosci 2003; 23: 5020-30.
136. Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC. FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol Dis 2004; 17: 435-44.
137. Almeida S, Laço M, Cunha-Oliveira T, Oliveira CR, Rego AC. BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons. Neurobiol Dis 2009; 35(3): 448-56.
138. Ferreira IL, Nascimento MV, Ribeiro M, et al. Mitochondrial-dependent apoptosis in Huntington's disease human cybrids. Exp Neurol 2010; 222: 243-55.
139. Knott AB, Bossy-Wetzel E. Impairing the mitochondrial fission and fusion balance: a new mechanism of neurodegeneration. Ann NY Acad Sci 2008; 1147: 283-92.
140. Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E. Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci 2008; 9: 505-18.
141. Reddy PH. Mitochondrial dysfunction in aging and Alzheimer's disease: strategies to protect neurons. Antioxid Redox Signal 2007; 9: 1647-58.
142. Olichon A, Emorine LJ, Descoins E, et al. The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 2002; 523: 171-6.
143. Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci USA 2004; 101: 15927-32.
144. Kim JY, Hwang JM, Ko HS, et al. Mitochondrial DNA content is decreased in autosomal dominant optic atrophy. Neurology 2005; 64(6): 966-72.
145. Meeusen S, DeVay R, Block J, et al. Mitochondrial inner-membrane fusion and crista maintenance requires the dynaminrelated GTPase Mgm1. Cell 2006; 127: 383-95.
146. Barsoum MJ, Yuan H, Gerencser AA, et al. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J 2006; 25: 3900-11.
147. Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA 2006; 103: 2653-8.
148. Jahani-Asl A, Cheung EC, Neuspiel M, et al. Mitofusin 2 protects cerebellar granule neurons against injury-induced cell death. J Biol Chem 2007; 282: 23788-98.
149. Smirnova E, Griparic L, Shurland DL, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 2001; 12: 2245-56.
150. Guinard AP, Song W, Bossy B, et al. In: Mutant huntingtin mediates neuronal injury by impairing mitochondrial fission and fusion balance, Nanosymposium, Society for Neuroscience, Chicago, USA, October 17-21, 2009; Book Four, pp. 4.
151. Orr AL, Li S, Wang CE, et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci 2008; 28: 2783-92.
152. Trushina E, Dyer RB, Badger JD II, et al. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 2004; 24: 8195-209.
153. Trushina E, Heldebrant MP, Perez-Terzic CM, et al. Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease. Proc Natl Acad Sci USA 2003; 100(21): 12171-6.
154. 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.
155. Gauthier LR, Charrin BC, Borrell-Pagès M, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004; 118(1): 127-38.
156. Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and OPA1 in apoptosis. Mol Biol Cell 2004; 15: 5001-11.
157. Karbowski M, Lee YJ, Gaume B, et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J Cell Biol 2002; 159: 931-8.
158. Chen H, McCaffery JM, Chan DC. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 2007; 130: 548-62.
159. Yuan H, Gerencser AA, Liot G, et al. Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons. Cell Death Differ 2007; 14: 462-71.
160. Alirol E, James D, Huber D, et al. The mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis. Mol Biol Cell 2006; 17: 4593-605.
161. Wasiak S, Zunino R, McBride HM. Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 2007; 177: 439-50.
162. Liot G, Bossy B, Lubitz S, et al. Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ 2009; 16: 899-909.
163. Wang H, Lim PJ, Karbowski M, Monteiro MJ. Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet 2009; 18: 737-52.
164. Gonatas NK, Stieber A, Gonatas JO. Fragmentation of the Golgi apparatus in neurodegenerative diseases and cell death. J Neurol Sci 2006; 246: 21-30.
165. Banoei MM, Houshmand M, Panahi MS, et al. Huntington's disease and mitochondrial DNA deletions: event or regular mechanism for mutant huntingtin protein and CAG repeats expansion?! Cell Mol Neurobiol 2007; 27: 867-75.
166. Acevedo-Torres K, Berríos L, Rosario N, et al. Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease. DNA Repair (Amst). 2009; 8: 126-36.
167. Liu CS, Cheng WL, Kuo SJ, et al. Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases. J Neurol Sci 2008; 264: 18-21.
168. Lee J, Kim CH, Simon DK, et al. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem 2005; 280: 40398-401.
169. Schaffar G, Breuer P, Boteva R, et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol Cell 2004; 15: 95-105.
170. Zhai W, Jeong H, Cui L, Krainc D, Tjian R. In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets. Cell 2005; 123: 1241-53.
171. Gerber HP, Seipel K, Georgiev O, et al. Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science 1994; 263: 808-11.
172. Sugars KL, Rubinsztein DC. Transcriptional abnormalities in Huntington disease. Trends Genet 2003; 5: 233-8.
173. Nucifora FC, Jr, Sasaki M, Peters MF, et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001; 291: 2423-8.
174. Steffan JS, Kazantsev A, Spasic-Boskovic O, et al. The Huntington's disease protein interacts with p53 and CBP and represses transcription. Proc Natl Acad Sci USA 2000; 97: 6763-8.
175. Bae B, Xu H, Igarashi S, et al. p53 mediates cellular dysfunction and behavior abnormalities in Huntington's disease. Neuron 2005; 47: 29-41.
176. Dunah AW, Jeong H, Griffin A, et al. Sp1 and TAF130 transcriptional activity disrupted in early Huntington's Disease. Science 2002; 296(5576): 2238-43.
177. Zuccato C, Tartari M, Crotti A, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 2003; 35: 76-83.
178. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003; 24: 78-90.
179. Cui L, Jeong H, Borovecki F, et al. Repression of PGC-1alpha gene transcription by mutant huntingtin leads to mitochondrial dysfunction in Huntington's disease. Cell 2006; 126: 59-69.
180. Weydt P, Pineda VV, Torrence AE, 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.
181. St-Pierre J, Drori S, Uldry M, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006; 127: 397-408.
182. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005; 1: 361-70.
183. Clark J, Simon DK. Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson's disease. Antioxid Redox Signal 2009; 11(3): 509-28.
184. Lee JM, Li J, Johnson DA, et al. Nrf2, a multi-organ protector? FASEB J 2005; 19(9): 1061-6.
185. Friling RS, Bensimon A, Tichauer Y, Daniel V. Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element. Proc Natl Acad Sci USA 1990; 87: 6258-62.
186. Favreau LV, Pickett CB. Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J Biol Chem 1991; 266: 4556-61.
187. Alam J, Camhi M, Choi M. Identification of a second region upstream of the mouse hemeoxygenase-1 gene that functions as a basal level and inducer-dependent transcription enhancer. J Biol Chem 1995; 270: 11977-84.
188. Feng Z, Jin S, Zupnick A, et al. p53 tumor suppressor protein regulates the levels of huntingtin gene expression. Oncogene 2006; 25: 1-7.
189. Suhr ST, Senut MC, Whitelegge JP, et al. Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J Cell Biol 2001; 153: 283-94.
190. Illuzzi J, Yerkes S, Parekh-Olmedo H, Kmiec EB. DNA breakage and induction of DNA damage response proteins precede the appearance of visible mutant huntingtin aggregates. J Neurosci Res 2009; 87(3): 733-47.
191. Powers WJ, Videen TO, Markham J, et al. Selective defect of in vivo glycolysis in early Huntington's disease striatum. Proc Natl Acad Sci USA 2007; 104: 2945-9.
192. Antonini A, Leenders KL, Spiegel R, et al. Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. Brain 1996; 119: 2085-95.
193. Mazziotta JC, Phelps ME, Pahl JJ, et al. Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease. N Engl J Med 1987; 316: 357-62.
194. Hayden MR, Martin WR, Stoessl AJ, et al. Positron emission tomography in the early diagnosis of Huntington's disease. Neurology 1986; 36: 888-94.
195. Kuhl DE, Phelps ME, Markham CH, et al. Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan. Ann Neurol 1982; 12: 425-34.
196. Berent S, Giordani B, Lehtinen S, et al. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function. Ann Neurol 1988; 23: 541-6.
197. Gamberino WC, Brennan WA Jr. Glucose transporter isoform expression in Huntington's disease brain. J Neurochem 1994; 63(4): 1392-7.
198. Feigin A, Tang C, Ma Y, et al. Thalamic metabolism and symptom onset in preclinical Huntington's disease. Brain 2007; 130: 2858-67.
199. Reynolds NC Jr, Prost RW, Mark LP. Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington's disease. Brain Res 2005; 1031: 82-9.
200. Ruocco HH, Lopes-Cendes I, Li LM, Cendes F. Evidence of thalamic dysfunction in Huntington disease by proton magnetic resonance spectroscopy. Mov Disord 2007; 22: 2052-6.
201. Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology 1993; 43: 2689-95.
202. Butterworth J, Yates CM, Reynolds GP. Distribution of phosphate-activated glutaminase, succinic dehydrogenase, pyruvate dehydrogenase and gamma-glutamyl transpeptidase in post-mortem brain from Huntington's disease and agonal cases. J Neurol Sci 1985; 67: 161-71.
203. Klivenyi P, Starkov AA, Calingasan NY, et al. Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicity. J Neurochem 2004; 88: 1352-60.
204. Brennan WA Jr, Bird ED, Aprille JR. Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 1985; 44: 1948-1950.
205. Gu M, Gash MT, Mann VM, et al. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol 1996; 39: 385-9.
206. Tabrizi SJ, Cleeter MW, Xuereb J, et al. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann Neurol 1999; 45: 25-32.
207. Benchoua A, Trioulier Y, Zala D, 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.
208. Guidetti P, Charles V, Chen EY, et al. Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp Neurol 2001; 169: 340-50.
209. Goebel HH, Heipertz R, Scholz W, Iqbal K, Tellez-Nagel I. Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies. Neurology 1978; 28: 23-31.
210. Graveland GA, Williams RS, DiFiglia M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 1985; 227: 770-3.
211. Saft C, Zange J, Andrich J, et al. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease. Mov Disord 2005; 20: 674-9.
212. Bogdanov MB, Andreassen OA, Dedeoglu A, Ferrante RJ, Beal MF. Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease. J Neurochem 2001; 79: 1246-9. Huntington's disease. Lancet 1989; 2: 979-80.
213. Reynolds GP, Pearson SJ. Increased brain 3-hydroxykynurenine in Huntington's disease. Lancet 1989; 2: 979-80.
214. 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.
215. Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression. PLoS One 2007; 2: e647.
216. Arenas J, Campos Y, Ribacoba R, et al. Complex I defect in muscle from patients with Huntington's disease. Ann Neurol 1998; 43: 397-400.
217. Almeida S, Sarmento-Ribeiro AB, Januário C, Rego AC, Oliveira CR. Evidence of apoptosis and mitochondrial abnormalities in peripheral blood cells of Huntington's disease patients. Biochem Biophys Res Commun 2008; 374: 599-603.
218. Djousse L, Knowlton B, Cupples LA, et al. Weight loss in early stage of Huntington's disease. Neurology 2002; 59: 1325-30.
219. Kirkwood SC, Su JL, Conneally P, Foroud T. Progression of symptoms in the early and middle stages of Huntington disease. Arch Neurol 2001; 58: 273-8.
220. Lanska DJ, Lavine L, Lanska MJ, Schoenberg BS. Huntington's disease mortality in the United States. Neurology 1988; 38: 769-72.
221. Trejo A, Boll MC, Alonso ME, Ochoa A, Velásquez L. Use of oral nutritional supplements in patients with Huntington's disease. Nutrition 2005; 21: 889-94.
222. Stoy N, McKay E. Weight loss in Huntington's disease. Ann Neurol 2000; 48: 130-1.
223. Kremer HP, Roos RA. Weight loss in Huntington's disease. Arch Neurol 1992; 49: 349.
224. Morales LM, Estévez J, Suárez H, et al. Nutritional evaluation of Huntington disease patients. Am J Clin Nutr 1989; 50: 145-50.
225. Van Raamsdonk JM, Gibson WT, Pearson J, et al. Body weight is modulated by levels of full-length huntingtin. Hum Mol Genet 2006; 15: 1513-23.
226. Phan J, Hickey MA, Zhang P, Chesselet MF, Reue K. Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models. Hum Mol Genet 2009; 18 (6): 1006-16.
227. Aziz NA, van der Marck MA, Pijl H, et al. Weight loss in neurodegenerative disorders. J Neurol 2008; 255: 1872-80.
228. Gaba AM, Zhang K, Marder K, et al. Energy balance in early-stage Huntington disease. Am J Clin Nutr 2005; 81: 1335-41.
229. Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's disease. Ann Neurol 2000; 47: 64-70.
230. Trejo A, Tarrats RM, Alonso ME, et al. Assessment of the nutrition status of patients with Huntington's disease. Nutrition 2004; 20: 192-196.
231. Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington's disease patients compared with matched controls. Med J Aust 1981; 1: 407-9.
232. Goodman AO, Murgatroyd PR, Medina-Gomez G, et al. The metabolic profile of early Huntington's disease - a combined human and transgenic mouse study. Exp Neurol 2008; 210: 691-8.
233. Myers RH, Sax DS, Koroshetz WJ, et al. Factors associated with slow progression in Huntington's disease. Arch Neurol 1991; 48: 800-4.
234. Lodi R, Schapira AH, Manners D, et al. Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann Neurol 2000; 48: 72-6.
235. van der Burg JM, Bacos K, Wood NI, et al. Increased metabolism in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 2008; 29: 41-51.
236. Pouladi MA, Xie Y, Skotte NH, et al. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Hum Mol Genet 2010; 19(8):1528-38.
237. Farrer LA. Diabetes mellitus in Huntington disease. Clin Genet 1985; 27: 62-7.
238. Podolsky S, Leopold NA, Sax DS. Increased frequency of diabetes mellitus in patients with Huntington's chorea. Lancet 1972; 1: 1356-8.
239. Podolsky S, Leopold NA. Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease. Gerontology 1977; 23: 55-63.
240. Lalic NM, Maric J, Svetel M, et al. Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch Neurol 2008; 65: 476-80.
241. Boesgaard TW, Nielsen TT, Josefsen K, et al. Huntington's disease does not appear to increase the risk of diabetes mellitus. J Neuroendocrinol 2009; 21(9): 770-6.
242. Andreassen OA, Dedeoglu A, Stanojevic V, et al. Huntington's disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression. Neurobiol Dis 2002; 11: 410-24.
243. Lüesse HG, Schiefer J, Spruenken A, et al. Evaluation of R6/2 HD transgenic mice for therapeutic studies in Huntington's disease: behavioral testing and impact of diabetes mellitus. Behav Brain Res 2001; 126: 185-95.
244. Hurlbert MS, Zhou W, Wasmeier C, et al. Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes. Diabetes 1999; 48: 649-51.
245. Björkqvist M, Fex M, Renström E, 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.
246. Björkqvist M, Petersén A, Bacos K, et al. Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2 transgenic mouse model of Huntington's disease. Hum Mol Genet 2006; 15: 1713-21.
247. Leblhuber F, Peichl M, Neubauer C, et al. Serum dehydroepiandrosterone and cortisol measurements in Huntington's chorea. J Neurol Sci 1995; 132: 76-9.
248. Mazurek MF, Garside S, Beal MF. Cortical peptide changes in Huntington's disease may be independent of striatal degeneration. Ann Neurol 1997; 41: 540-7.
249. Markianos M, Panas M, Kalfakis N, Vassilopoulos D. Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia. Ann Neurol 2005; 57: 520-5.
250. Aziz NA, Pijl H, Frölich M, et al. Growth hormone and ghrelin secretion are associated with clinical severity in Huntington's disease. Eur J Neurol 2009; 17: 280-8.
251. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 1999; 22: 221-32.
252. Björkqvist M, Leavitt B, Nielsen J, et al. Cocaine and amphetamine regulated transcript is increased in Huntington disease. Movement Disorders 2007; 22: 1952-54.
253. Parker WD Jr, Boyson SJ, Luder AS, Parks JK. Evidence for a defect in NADH:ubiquinone oxidoreductase (complex I) in Huntington's disease. Neurology 1990; 40: 1231-4.
254. Turner C, Cooper JM, Schapira AH. Clinical correlates of mitochondrial function in Huntington's disease muscle. Mov Disord 2007; 22: 1715-21.
255. Gizatullina ZZ, Lindenberg KS, Harjes P, et al. Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice. Ann Neurol 2006; 59: 407-11.
256. Ciammola A, Sassone J, Alberti L, et al. Increased apoptosis, Huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington's disease subjects. Cell Death Differ 2006; 13: 2068-78.
257. Squitieri F, Cannella M, Sgarbi G, et al. Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 2006; 127: 217-20.
258. Panov AV, Lund S, Greenamyre JT. Ca2+-induced permeability transition in human lymphoblastoid cell mitochondria from normal and Huntington's disease individuals. Mol Cell Biochem 2005; 269(1-2): 143-52.