Mechanisms of RNA-induced toxicity in CAG repeat disorders

Cell Death and Disease

Volumn 4, Issue 8, 2013, Pages

  Nalavade, R ^a   Griesche, N ^a   Ryan, D P ^a   Hildebrand, S ^b   Krauss S ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b UNIVERSITY OF BONN   (Germany)

Author keywords

CAG repeats; Neurodegeneration; Polyglutamine diseases; RNA mediated toxicity; RNA protein interactions

Indexed keywords

ANTIDEPRESSANT AGENT; DOUBLE STRANDED RNA; MESSENGER RNA; MOOD STABILIZER; MUSCLEBLIND LIKE 1 PROTEIN; MYOTONIC DYSTROPHY PROTEIN KINASE; NEUROLEPTIC AGENT; NUCLEOLIN; POLYGLUTAMINE; RIBOSOME RNA; RNA BINDING PROTEIN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; CAG REPEAT; CAG REPEAT DISORDER; CELLULAR DISTRIBUTION; CEREBELLAR ATAXIA; CHOREOATHETOSIS; COGNITIVE DEFECT; CONFORMATIONAL TRANSITION; DEGENERATIVE DISEASE; DEMENTIA; DENTATORUBROPALLIDOLUYSIAN ATROPHY; DISEASE COURSE; DYSARTHRIA; DYSPHAGIA; EXTRAPYRAMIDAL SYMPTOM; EYE MOVEMENT DISORDER; GENE EXPRESSION; GENETIC CODE; GENETIC REGULATION; GENETIC TRANSCRIPTION; HUMAN; HUNTINGTON CHOREA; KENNEDY DISEASE; MENTAL DEFICIENCY; MENTAL DISEASE; MOTOR DYSFUNCTION; MYOCLONUS EPILEPSY; MYOTONIC DYSTROPHY; NERVE CELL DEGENERATION; NERVE DEGENERATION; NERVOUS SYSTEM DEVELOPMENT; NEUROLOGIC DISEASE; NEUROTOXICITY; NONHUMAN; OPHTHALMOPLEGIA; PATHOGENESIS; PERIPHERAL NEUROPATHY; PHYSIOTHERAPY; POLYGLUTAMINE DISEASE; POSTTRANSCRIPTIONAL GENE SILENCING; PRIORITY JOURNAL; PROTEIN SECONDARY STRUCTURE; PSYCHOSIS; REVIEW; RNA FOLDING; RNA INTERFERENCE; RNA STRUCTURE; SPEECH THERAPY; SPINOCEREBELLAR DEGENERATION; SPLICEOSOME; START CODON; STEM CELL TRANSPLANTATION; UNTRANSLATED REGION; VISUAL DISORDER;

EID: 84882589462     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2013.276     Document Type: Review

References (110)

1. Jasinska A, Krzyzosiak WJ. Repetitive sequences that shape the human transcriptome. FEBS Lett 2004; 567: 136-141 (Pubitemid 38686436)
2. Mirkin SM. Expandable DNA repeats and human disease. Nature 2007; 447: 932-940 (Pubitemid 46975760)
3. Liu G, Leffak M. Instability of (CTG)n (CAG)n trinucleotide repeats and DNA synthesis. Cell Biosci 2012; 2: 7
4. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007; 30: 575-621 (Pubitemid 47218768)
5. Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol 2010; 67: 291-300
6. Nakamori M, Thornton C. Epigenetic changes and non-coding expanded repeats. Neurobiol Dis 2010; 39: 21-27
7. Luheshi LM, Dobson CM. Bridging the gap: From protein misfolding to protein misfolding diseases. FEBS Lett 2009; 583: 2581-2586
8. Rubinsztein DC. Lessons from animal models of Huntington's disease. Trends Genet 2002; 18: 202-209 (Pubitemid 34273741)
9. Perutz MF. Glutamine repeats and neurodegenerative diseases: Molecular aspects. Trends Biochem Sci 1999; 24: 58-63 (Pubitemid 29346574)
10. Cummings CJ, Zoghbi HY. Trinucleotide repeats: Mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 2000; 1: 281-328
11. Ross CA. Polyglutamine pathogenesis: Emergence of unifying mechanisms for Huntington's disease and related disorders. Neuron 2002; 35: 819-822
12. Michalik A, Van Broeckhoven C. Pathogenesis of polyglutamine disorders: Aggregation revisited. Hum Mol Genet 2003; 12: R173-R186 (Pubitemid 37259330)
13. Bano D, Zanetti F, Mende Y, Nicotera P. Neurodegenerative processes in Huntington's disease. Cell Death Dis 2011; 2: E228
14. Jimenez-Sanchez M, Thomson F, Zavodszky E, Rubinsztein DC. Autophagy and polyglutamine diseases. Prog Neurobiol 2012; 97: 67-82
15. Li LB, Yu Z, Teng X, Bonini NM. RNA toxicity is a component of ataxin-3 degeneration in Drosophila. Nature 2008; 453: 1107-1111 (Pubitemid 351871727)
16. Sobczak K,, de Mezer M, Michlewski G, Krol J, Krzyzosiak WJ. RNA structure of trinucleotide repeats associated with human neurological diseases. Nucleic Acids Res 2003; 31: 5469-5482 (Pubitemid 37441917)
17. Romeo V. Myotonic dystrophy type 1 or Steinert's disease. Adv Exp Med Biol 2012; 724: 239-257
18. Napierala M, Krzyzosiak WJ. CUG repeats present in myotonin kinase RNA form metastable "slippery" hairpins. J Biol Chem 1997; 272: 31079-31085 (Pubitemid 27527556)
19. Galvao R, Mendes-Soares L, Camara J, Jaco I, Carmo-Fonseca M. Triplet repeats, RNA secondary structure and toxic gain-of-function models for pathogenesis. Brain Res Bull 2001; 56: 191-201 (Pubitemid 33062342)
20. Sobczak K, Krzyzosiak WJ. CAG repeats containing CAA interruptions form branched hairpin structures in spinocerebellar ataxia type 2 transcripts. J Biol Chem 2005; 280: 3898-3910 (Pubitemid 40223859)
21. Sobczak K, Krzyzosiak WJ. Imperfect CAG repeats form diverse structures in SCA1 transcripts. J Biol Chem 2004; 279: 41563-41572 (Pubitemid 39313598)
22. de Mezer M, Wojciechowska M, Napierala M, Sobczak K, Krzyzosiak WJ. Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference. Nucleic Acids Res 2011; 39: 3852-3863
23. Kiliszek A, Kierzek R, Krzyzosiak WJ, Rypniewski W. Atomic resolution structure of CAG RNA repeats: Structural insights and implications for the trinucleotide repeat expansion diseases. Nucleic Acids Res 2010; 38: 8370-8376
24. Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML, Ebner TJ et al. RNA gainof-function in spinocerebellar ataxia type 8. PLoS Genet 2009; 5: E1000600
25. Matsuura T, Yamagata T, Burgess DL, Rasmussen A, Grewal RP, Watase K et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000; 26: 191-194
26. Holmes SE, ÓHearn EE, McInnis MG, Gorelick-Feldman DA, Kleiderlein JJ, Callahan C et al. Expansion of a novel CAG trinucleotide repeat in the 50 region of PPP2R2B is associated with SCA12. Nat Genet 1999; 23: 391-392
27. ÓHearn E, Holmes SE, Margolis RL. Spinocerebellar ataxia type 12. Handb Clin Neurol 2012; 103: 535-547
28. Wang LC, Chen KY, Pan H, Wu CC, Chen PH, Liao YT et al. Muscleblind participates in RNA toxicity of expanded CAG and CUG repeats in Caenorhabditis elegans. Cell Mol Life Sci 2011; 68: 1255-1267
29. McLeod CJ, ÓKeefe LV, Richards RI. The pathogenic agent in Drosophila models of 'polyglutamine' diseases. Hum Mol Genet 2005; 14: 1041-1048 (Pubitemid 40575879)
30. Hsu RJ, Hsiao KM, Lin MJ, Li CY, Wang LC, Chen LK et al. Long tract of untranslated CAG repeats is deleterious in transgenic mice. PLoS One 2011; 6: E16417
31. Ho TH, Charlet BN, Poulos MG, Singh G, Swanson MS, Cooper TA. Muscleblind proteins regulate alternative splicing. EMBO J 2004; 23: 3103-3112 (Pubitemid 39093604)
32. Kino Y, Mori D, Oma Y, Takeshita Y, Sasagawa N, Ishiura S. Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. Hum Mol Genet 2004; 13: 495-507 (Pubitemid 38313209)
33. Wang ET, Cody NA, Jog S, Biancolella M, Wang TT, Treacy DJ et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell 2012; 150: 710-724
34. Warf MB, Diegel JV, von Hippel PH, Berglund JA. The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing. Proc Natl Acad Sci USA 2009; 106: 9203-9208
35. Yuan Y, Compton SA, Sobczak K, Stenberg MG, Thornton CA, Griffith JD et al. Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res 2007; 35: 5474-5486 (Pubitemid 47423921)
36. Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA et al. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J 2000; 19: 4439-4448
37. Fardaei M, Larkin K, Brook JD, Hamshere MG. In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts. Nucleic Acids Res 2001; 29: 2766-2771 (Pubitemid 32685039)
38. Mankodi A, Urbinati CR, Yuan QP, Moxley RT, Sansone V, Krym M et al. Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. Hum Mol Genet 2001; 10: 2165-2170 (Pubitemid 32998828)
39. Jiang H, Mankodi A, Swanson MS, Moxley RT, Thornton CA. Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons. Hum Mol Genet 2004; 13: 3079-3088 (Pubitemid 40045262)
40. Lin X, Miller JW, Mankodi A, Kanadia RN, Yuan Y, Moxley RT et al. Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet 2006; 15: 2087-2097 (Pubitemid 43923398)
41. Jog SP, Paul S, Dansithong W, Tring S, Comai L, Reddy S. RNA splicing is responsive to MBNL1 dose. PLoS One 2012; 7: E48825
42. Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D et al. A muscleblind knockout model for myotonic dystrophy. Science 2003; 302: 1978-1980 (Pubitemid 37523508)
43. Suenaga K, Lee KY, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H et al. Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. PLoS One 2012; 7: E33218
44. Mykowska A, Sobczak K, Wojciechowska M, Kozlowski P, Krzyzosiak WJ. CAG repeats mimic CUG repeats in the misregulation of alternative splicing. Nucleic Acids Res 2011; 39: 8938-8951
45. Tsoi H, Lau TC, Tsang SY, Lau KF, Chan HY. CAG expansion induces nucleolar stress in polyglutamine diseases. Proc Natl Acad Sci USA 2012; 109: 13428-13433
46. Tsoi H, Chan HY. Expression of expanded CAG transcripts triggers nucleolar stress in Huntington's disease. Cerebellum 2013; 12: 310-312
47. Zhang Y, Lu H. Signaling to p53: Ribosomal proteins find their way. Cancer Cell 2009; 16: 369-377
48. van Eyk CL, ÓKeefe LV, Lawlor KT, Samaraweera SE, McLeod CJ, Price GR et al. Perturbation of the Akt/Gsk3-beta signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs. Hum Mol Genet 2011; 20: 2783-2794
49. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391: 806-811 (Pubitemid 28099681)
50. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001; 409: 363-366 (Pubitemid 32151243)
51. Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-Transcriptional gene silencing in Drosophila cells. Nature 2000; 404: 293-296 (Pubitemid 30163547)
52. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2 a link between genetic and biochemical analyses of RNAi. Science 2001; 293: 1146-1150 (Pubitemid 32758097)
53. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000; 101: 25-33
54. Handa V, Saha T, Usdin K. The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 2003; 31: 6243-6248 (Pubitemid 37442352)
55. Krol J, Fiszer A, Mykowska A, Sobczak K, de Mezer M, Krzyzosiak WJ. Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Mol Cell 2007; 25: 575-586 (Pubitemid 46274449)
56. Banez-Coronel M, Porta S, Kagerbauer B, Mateu-Huertas E, Pantano L, Ferrer I et al. A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity. PLoS Genet 2012; 8: E1002481
57. He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW. The antisense transcriptomes of human cells. Science 2008; 322: 1855-1857
58. Faghihi MA, Wahlestedt C. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 2009; 10: 637-643
59. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M et al. Antisense transcription in the mammalian transcriptome. Science 2005; 309: 1564-1566
60. Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 2006; 38: 758-769 (Pubitemid 43980596)
61. Wilburn B, Rudnicki DD, Zhao J, Weitz TM, Cheng Y, Gu X et al. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron 2011; 70: 427-440
62. Seixas AI, Holmes SE, Takeshima H, Pavlovich A, Sachs N, Pruitt JL et al. Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis. Ann Neurol 2012; 71: 245-257
63. Yu Z, Teng X, Bonini NM. Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy. PLoS Genet 2011; 7: E1001340
64. Lawlor KT, ÓKeefe LV, Samaraweera SE, van Eyk CL, McLeod CJ, Maloney CA et al. Double-stranded RNA is pathogenic in Drosophila models of expanded repeat neurodegenerative diseases. Hum Mol Genet 2011; 20: 3757-3768
65. Williams BR. PKR; a sentinel kinase for cellular stress. Oncogene 1999; 18: 6112-6120
66. Tian B, White RJ, Xia T, Welle S, Turner DH, Mathews MB et al. Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR. RNA 2000; 6: 79-87 (Pubitemid 30069038)
67. Peel AL, Rao RV, Cottrell BA, Hayden MR, Ellerby LM, Bredesen DE. Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue. Hum Mol Genet 2001; 10: 1531-1538 (Pubitemid 32734304)
68. Bando Y, Onuki R, Katayama T, Manabe T, Kudo T, Taira K et al. Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease. Neurochem Int 2005; 46: 11-18 (Pubitemid 39572782)
69. Liu CR, Chang CR, Chern Y, Wang TH, Hsieh WC, Shen WC et al. Spt4 is selectively required for transcription of extended trinucleotide repeats. Cell 2012; 148: 690-701
70. Krau S, Griesche N, Jastrzebska E, Chen C, Rutschow Ds, AchmO1ller C et al. Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1,Ä ìPP2A protein complex. Nat Commun [10.1038/ncomms2514] 2013; 4: 1511
71. Trockenbacher A, Suckow V, Foerster J, Winter J, Krauss S, Ropers HH et al. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet 2001; 29: 287-294 (Pubitemid 33096453)
72. Liu E, Knutzen CA, Krauss S, Schweiger S, Chiang GG. Control of mTORC1 signaling by the Opitz syndrome protein MID1. Proc Natl Acad Sci USA 2011; 108: 8680-8685
73. Aranda-Orgilles B, Rutschow D, Zeller R, Karagiannidis AI, Koehler A, Chen C et al. The PP2a-specific ubiquitin ligase Mid1 is a sequence-dependent regulator of translation efficiency controlling 3-phosphoinositide dependent protein kinase-1 (PDPK-1). J Biol Chem 2011; 286: 39945-39957
74. Aranda-Orgilles B, Trockenbacher A, Winter J, Aigner J, Kohler A, Jastrzebska E et al. The Opitz syndrome gene product MID1 assembles a microtubule-Associated ribonucleoprotein complex. Hum Genet 2008; 123: 163-176
75. Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA 2011; 108: 260-265
76. Pearson CE. Repeat associated non-ATG translation initiation: One DNA, two transcripts, seven reading frames, potentially nine toxic entities! PLoS Genet 2011; 7: E1002018
77. Wojciechowska M, Krzyzosiak WJ. Cellular toxicity of expanded RNA repeats: Focus on RNA foci. Hum Mol Genet 2011; 20: 3811-3821
78. Ho TH, Savkur RS, Poulos MG, Mancini MA, Swanson MS, Cooper TA. Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy. J Cell Sci 2005; 118: 2923-2933 (Pubitemid 41136369)
79. Tsoi H, Lau CK, Lau KF, Chan HY. Perturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in polyQ diseases. Hum Mol Genet 2011; 20: 3787-3797
80. Zuccato C, Valenza M, Cattaneo E. Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol Rev 2010; 90: 905-981
81. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 2004; 10: 148-154 (Pubitemid 38524884)
82. Butler DC, McLear JA, Messer A. Engineered antibody therapies to counteract mutant huntingtin and related toxic intracellular proteins. Prog Neurobiol 2012; 97: 190-204
83. Lecerf JM, Shirley TL, Zhu Q, Kazantsev A, Amersdorfer P, Housman DE et al. Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease. Proc Natl Acad Sci USA 2001; 98: 4764-4769 (Pubitemid 32295050)
84. Wolfgang WJ, Miller TW, Webster JM, Huston JS, Thompson LM, Marsh JL et al. Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies. Proc Natl Acad Sci USA 2005; 102: 11563-11568 (Pubitemid 41153859)
85. Bortvedt SF, McLear JA, Messer A, Ahern-Rindell AJ, Wolfgang WJ. Cystamine and intrabody co-Treatment confers additional benefits in a fly model of Huntington's disease. Neurobiol Dis 2010; 40: 130-134
86. Hochfeld WE, Lee S, Rubinsztein DC. Therapeutic induction of autophagy to modulate neurodegenerative disease progression. Acta Pharmacol Sin 2013; 34: 600-604
87. Tanaka F, Katsuno M, Banno H, Suzuki K, Adachi H, Sobue G. Current status of treatment of spinal and bulbar muscular atrophy. Neural Plast 2012; 2012: 369284
88. Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 2010; 133: 93-104
89. Rose C, Menzies FM, Renna M, Acevedo-Arozena A, Corrochano S, Sadiq O et al. Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease. Hum Mol Genet 2010; 19: 2144-2153
90. Ravikumar B, Duden R, Rubinsztein DC. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 2002; 11: 1107-1117 (Pubitemid 34521091)
91. Adachi H, Katsuno M, Minamiyama M, Sang C, Pagoulatos G, Angelidis C et al. Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J Neurosci 2003; 23: 2203-2211 (Pubitemid 36368908)
92. Tokui K, Adachi H, Waza M, Katsuno M, Minamiyama M, Doi H et al. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse. Hum Mol Genet 2009; 18: 898-910
93. Nagashima Y, Kowa H, Tsuji S, Iwata A. FAT10 protein binds to polyglutamine proteins and modulates their solubility. J Biol Chem 2011; 286: 29594-29600
94. Reuter I, Tai YF, Pavese N, Chaudhuri KR, Mason S, Polkey CE et al. Long-Term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington's disease. J Neurol Neurosurg Psychiatry 2008; 79: 948-951
95. Benraiss A, Goldman SA. Cellular therapy and induced neuronal replacement for Huntington's disease. Neurotherapeutics 2011; 8: 577-590
96. Chang YK, Chen MH, Chiang YH, Chen YF, Ma WH, Tseng CY et al. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. J Biomed Sci 2011; 18: 54
97. Benraiss A, Bruel-Jungerman E, Lu G, Economides AN, Davidson B, Goldman SA. Sustained induction of neuronal addition to the adult rat neostriatum by AAV4-delivered noggin and BDNF. Gene Ther 2012; 19: 483-493
98. Meisner F, Scheller C, Kneitz S, Sopper S, Neuen-Jacob E, Riederer P et al. Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: A novel pharmacological action of memantine. Neuropsychopharmacology 2008; 33: 2228-2236 (Pubitemid 351992085)
99. Zigova T, Pencea V, Wiegand SJ, Luskin MB. Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 1998; 11: 234-245 (Pubitemid 28361411)
100. Borrell-Pages M, Canals JM, Cordelieres 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: 1410-1424
101. Naia L, Ribeiro MJ, Rego AC. Mitochondrial and metabolic-based protective strategies in Huntington's disease: The case of creatine and coenzyme Q. Rev Neurosci 2012; 23: 13-28
102. Chen X, Wu J, Lvovskaya S, Herndon E, Supnet C, Bezprozvanny I. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model. Mol Neurodegener 2011; 6: 81
103. Johri A, Beal MF. Antioxidants in Huntington's disease. Biochim Biophys Acta 2012; 1822: 664-674
104. Pallos J, Bodai L, Lukacsovich T, Purcell JM, Steffan JS, Thompson LM et al. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. Hum Mol Genet 2008; 17: 3767-3775
105. Ferrante RJ, Ryu H, Kubilus JK, D'Mello S, Sugars KL, Lee J et al. Chemotherapy for the brain: The antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J Neurosci 2004; 24: 10335-10342 (Pubitemid 39552617)
106. Zhang Y, Friedlander RM. Using non-coding small RNAs to develop therapies for Huntington's disease. Gene Ther 2011; 18: 1139-1149
107. Ramachandran PS, Keiser MS, Davidson BL. Recent Advances in RNA Interference Therapeutics for CNS Diseases. Neurotherapeutics 2013; 10: 473-485
108. Scholefield J, Greenberg LJ, Weinberg MS, Arbuthnot PB, Abdelgany A, Wood MJ. Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype. PLoS One 2009; 4: E7232
109. McBride JL, Pitzer MR, Boudreau RL, Dufour B, Hobbs T, Ojeda SR et al. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Mol Ther 2011; 19: 2152-2162
110. Boudreau RL, McBride JL, Martins I, Shen S, Xing Y, Carter BJ et al. Nonallele-specific silencing of mutant and wild-Type Huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol Ther 2009; 17: 1053-1063