REFERENCES
4. Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. CAG repeat not polyglutamine length determines timing of Huntington’s disease onset. Cell 2019;178:887-900.e14.
5. Handsaker RE, Kashin S, Reed NM, et al. Long somatic DNA-repeat expansion drives neurodegeneration in Huntington disease. bioRXiv. [Preprint.] May 20, 2024 [accessed 2024 Aug 6]. Available from: https://www.biorxiv.org/content/10.1101/2024.05.17.592722v1.
6. DiFiglia M, Leavitt BR, Macdonald D, Thompson LM; Huntington’s Disease Nomenclature Working Group. Towards standardizing nomenclature in Huntington’s disease research. J Huntingtons Dis 2024;13:119-31.
7. 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;119:46-71.
8. DiFiglia M. Excitotoxic injury of the neostriatum: a model for Huntington’s disease. Trends Neurosci 1990;13:286-9.
10. Chuang CL, Demontis F. Systemic manifestation and contribution of peripheral tissues to Huntington’s disease pathogenesis. Ageing Res Rev 2021;69:101358.
11. Weiss A, Träger U, Wild EJ, et al. Mutant huntingtin fragmentation in immune cells tracks Huntington’s disease progression. J Clin Invest 2012;122:3731-6.
12. Sulston JE. Neuronal cell lineages in the nematode Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol 1983;48:443-52.
13. Gonzalez-Moragas L, Roig A, Laromaine A. C. elegans as a tool for in vivo nanoparticle assessment. Adv Colloid Interface Sci 2015;219:10-26.
14. The C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 1998;282:2012-8.
15. Rieckher M, Tavernarakis N. Generation of Caenorhabditis elegans transgenic animals by DNA microinjection. Bio Protoc 2017;7:e2565.
16. Parker JA, Connolly JB, Wellington C, Hayden M, Dausset J, Neri C. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death. Proc Natl Acad Sci U S A 2001;98:13318-23.
17. Morley JF, Brignull HR, Weyers JJ, Morimoto RI. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A 2002;99:10417-22.
18. Satyal SH, Schmidt E, Kitagawa K, et al. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci U S A 2000;97:5750-5.
19. Faber PW, Alter JR, MacDonald ME, Hart AC. Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci U S A 1999;96:179-84.
20. Faber PW, Voisine C, King DC, Bates EA, Hart AC. Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity. Proc Natl Acad Sci U S A 2002;99:17131-6.
21. Voisine C, Varma H, Walker N, Bates EA, Stockwell BR, Hart AC. Identification of potential therapeutic drugs for huntington’s disease using Caenorhabditis elegans. PLoS One 2007;2:e504.
22. Cordeiro LM, Machado ML, da Silva AF, et al. Rutin protects Huntington’s disease through the insulin/IGF1 (IIS) signaling pathway and autophagy activity: study in Caenorhabditis elegans model. Food Chem Toxicol 2020;141:111323.
23. Cordeiro LM, Soares MV, da Silva AF, et al. Neuroprotective effects of rutin on ASH neurons in Caenorhabditis elegans model of Huntington’s disease. Nutr Neurosci 2022;25:2288-301.
24. Cordeiro LM, Soares MV, da Silva AF, et al. Toxicity of copper and zinc alone and in combination in Caenorhabditis elegans model of Huntington’s disease and protective effects of rutin. Neurotoxicology 2023;97:120-32.
25. Zeng Y, Guo W, Xu G, et al. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease. Drug Des Devel Ther 2016;10:1443-51.
26. Bicca Obetine Baptista F, Arantes LP, Machado ML, et al. Diphenyl diselenide protects a Caenorhabditis elegans model for Huntington’s disease by activation of the antioxidant pathway and a decrease in protein aggregation. Metallomics 2020;12:1142-58.
27. Venken KJ, Simpson JH, Bellen HJ. Genetic manipulation of genes and cells in the nervous system of the fruit fly. Neuron 2011;72:202-30.
28. Pfeiffer BD, Jenett A, Hammonds AS, et al. Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci U S A 2008;105:9715-20.
29. Ugur B, Chen K, Bellen HJ. Drosophila tools and assays for the study of human diseases. Dis Model Mech 2016;9:235-44.
30. Chan HY, Bonini NM. Drosophila models of human neurodegenerative disease. Cell Death Differ 2000;7:1075-80.
31. Thaker HM, Kankel DR. Mosaic analysis gives an estimate of the extent of genomic involvement in the development of the visual system in Drosophila melanogaster. Genetics 1992;131:883-94.
32. Masse NY, Turner GC, Jefferis GS. Olfactory information processing in Drosophila. Curr Biol 2009;19:R700-13.
33. Amrein H, Thorne N. Gustatory perception and behavior in Drosophila melanogaster. Curr Biol 2005;15:R673-84.
34. Kamikouchi A, Inagaki HK, Effertz T, et al. The neural basis of Drosophila gravity-sensing and hearing. Nature 2009;458:165-71.
35. Song W, Onishi M, Jan LY, Jan YN. Peripheral multidendritic sensory neurons are necessary for rhythmic locomotion behavior in Drosophila larvae. Proc Natl Acad Sci U S A 2007;104:5199-204.
36. McGurk L, Berson A, Bonini NM. Drosophila as an in vivo model for human neurodegenerative disease. Genetics 2015;201:377-402.
37. Yamamoto S, Jaiswal M, Charng WL, et al. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell 2014;159:200-14.
38. Lessing D, Bonini NM. Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants. Nat Rev Genet 2009;10:359-70.
39. Rosas-Arellano A, Estrada-Mondragón A, Piña R, Mantellero CA, Castro MA. The tiny drosophila melanogaster for the biggest answers in Huntington’s disease. Int J Mol Sci 2018;19:2398.
40. Romero E, Cha GH, Verstreken P, et al. Suppression of neurodegeneration and increased neurotransmission caused by expanded full-length huntingtin accumulating in the cytoplasm. Neuron 2008;57:27-40.
41. Steffan JS, Bodai L, Pallos J, et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001;413:739-43.
42. Xu F, Kula-Eversole E, Iwanaszko M, Hutchison AL, Dinner A, Allada R. Circadian clocks function in concert with heat shock organizing protein to modulate mutant huntingtin aggregation and toxicity. Cell Rep 2019;27:59-70.e4.
43. Wang CE, Tydlacka S, Orr AL, et al. Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington’s disease. Hum Mol Genet 2008;17:2738-51.
44. Chongtham A, Yoo JH, Chin TM, et al. Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila model. Front Neurosci 2022;16:902205.
45. Arabit JGJ, Elhaj R, Schriner SE, Sevrioukov EA, Jafari M. Rhodiola rosea improves lifespan, locomotion, and neurodegeneration in a Drosophila melanogaster model of Huntington’s disease. Biomed Res Int 2018;2018:6726874.
47. Bandmann O, Burton EA. Genetic zebrafish models of neurodegenerative diseases. Neurobiol Dis 2010;40:58-65.
48. Karlovich CA, John RM, Ramirez L, Stainier DY, Myers RM. Characterization of the Huntington’s disease (HD) gene homologue in the zebrafish Danio rerio. Gene 1998;217:117-25.
49. Lumsden AL, Henshall TL, Dayan S, Lardelli MT, Richards RI. Huntingtin-deficient zebrafish exhibit defects in iron utilization and development. Hum Mol Genet 2007;16:1905-20.
50. Miller VM, Nelson RF, Gouvion CM, et al. CHIP suppresses polyglutamine aggregation and toxicity in vitro and in vivo. J Neurosci 2005;25:9152-61.
51. VerPlank JJS, Tyrkalska SD, Fleming A, Rubinsztein DC, Goldberg AL. cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases. Proc Natl Acad Sci U S A 2020;117:14220-30.
52. Lucini C, D’Angelo L, Cacialli P, Palladino A, de Girolamo P. BDNF, Brain, and regeneration: insights from zebrafish. Int J Mol Sci 2018;19:3155.
53. Conforti P, Mas Monteys A, Zuccato C, Buckley NJ, Davidson B, Cattaneo E. In vivo delivery of DN:REST improves transcriptional changes of REST-regulated genes in HD mice. Gene Ther 2013;20:678-85.
54. Yu C, Li CH, Chen S, Yoo H, Qin X, Park H. Decreased BDNF release in cortical neurons of a knock-in mouse model of Huntington’s disease. Sci Rep 2018;8:16976.
55. 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.
56. Rattray I, Smith EJ, Crum WR, et al. Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington’s disease. PLoS One 2013;8:e84726.
57. 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.
58. Carter RJ, Lione LA, Humby T, et al. Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 1999;19:3248-57.
59. Cheng PH, Li CL, Her LS, et al. Significantly differential diffusion of neuropathological aggregates in the brain of transgenic mice carrying N-terminal mutant huntingtin fused with green fluorescent protein. Brain Struct Funct 2013;218:283-94.
60. Gray M, Shirasaki DI, Cepeda C, et al. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 2008;28:6182-95.
61. Kotliarova S, Jana NR, Sakamoto N, et al. Decreased expression of hypothalamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine-EGFP fluorescent aggregates. J Neurochem 2005;93:641-53.
62. Tebbenkamp AT, Xu G, Siemienski ZB, et al. Experimental mutagenesis of huntingtin to map cleavage sites: different outcomes in cell and mouse models. J Huntingtons Dis 2014;3:73-86.
63. Tebbenkamp AT, Swing D, Tessarollo L, Borchelt DR. Premature death and neurologic abnormalities in transgenic mice expressing a mutant huntingtin exon-2 fragment. Hum Mol Genet 2011;20:1633-42.
64. Stricker-Shaver J, Novati A, Yu-Taeger L, Nguyen HP. Genetic rodent models of huntington disease. Adv Exp Med Biol 2018;1049:29-57.
65. Tebbenkamp AT, Green C, Xu G, et al. Transgenic mice expressing caspase-6-derived N-terminal fragments of mutant huntingtin develop neurologic abnormalities with predominant cytoplasmic inclusion pathology composed largely of a smaller proteolytic derivative. Hum Mol Genet 2011;20:2770-82.
66. Reddy PH, Williams M, Charles V, et al. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 1998;20:198-202.
67. 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.
68. Benn CL, Slow EJ, Farrell LA, et al. Glutamate receptor abnormalities in the YAC128 transgenic mouse model of Huntington’s disease. Neuroscience 2007;147:354-72.
69. Hodgson JG, Agopyan N, Gutekunst CA, et al. A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999;23:181-92.
70. 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.
71. Van Raamsdonk JM, Pearson J, Slow EJ, Hossain SM, Leavitt BR, Hayden MR. Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington’s disease. J Neurosci 2005;25:4169-80.
72. Kennedy L, Shelbourne PF, Dewar D. Alterations in dopamine and benzodiazepine receptor binding precede overt neuronal pathology in mice modelling early Huntington disease pathogenesis. Brain Res 2005;1039:14-21.
73. Shelbourne PF, Killeen N, Hevner RF, et al. A Huntington’s disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum Mol Genet 1999;8:763-74.
74. Menalled LB, Sison JD, Dragatsis I, Zeitlin S, Chesselet MF. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington’s disease with 140 CAG repeats. J Comp Neurol 2003;465:11-26.
75. Wheeler VC, Gutekunst CA, Vrbanac V, et al. Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice. Hum Mol Genet 2002;11:633-40.
76. Wheeler VC, White JK, Gutekunst 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.
77. Heng MY, Tallaksen-Greene SJ, Detloff PJ, Albin RL. Longitudinal evaluation of the Hdh(CAG)150 knock-in murine model of Huntington’s disease. J Neurosci 2007;27:8989-98.
78. Tallaksen-Greene SJ, Crouse AB, Hunter JM, Detloff PJ, Albin RL. Neuronal intranuclear inclusions and neuropil aggregates in HdhCAG(150) knockin mice. Neuroscience 2005;131:843-52.
79. Lin CH, Tallaksen-Greene S, Chien WM, et al. Neurological abnormalities in a knock-in mouse model of Huntington’s disease. Hum Mol Genet 2001;10:137-44.
80. Levine MS, Cepeda C, Hickey MA, Fleming SM, Chesselet MF. Genetic mouse models of Huntington’s and Parkinson’s diseases: illuminating but imperfect. Trends Neurosci 2004;27:691-7.
81. Yu ZX, Li SH, Evans J, Pillarisetti A, Li H, Li XJ. Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington’s disease. J Neurosci 2003;23:2193-202.
82. Gardian G, Browne SE, Choi DK, et al. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease. J Biol Chem 2005;280:556-63.
83. Kong G, Cao KL, Judd LM, Li S, Renoir T, Hannan AJ. Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington’s disease. Neurobiol Dis 2020;135:104268.
84. Tong X, Ao Y, Faas GC, et al. Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat Neurosci 2014;17:694-703.
85. Abjean L, Ben Haim L, Riquelme-Perez M, et al. Reactive astrocytes promote proteostasis in Huntington’s disease through the JAK2-STAT3 pathway. Brain 2023;146:149-66.
86. 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.
87. van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ. Delaying the onset of Huntington’s in mice. Nature 2000;404:721-2.
88. 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.
89. Willner P. Methods for assessing the validity of animal models of human psychopathology. In: Boulton AA, Baker GB, Martin-Iverson MT, editors. Animal models in psychiatry, I. Neuromethods, vol 18. Humana Press; 1991.
90. Jacobsen JC, Bawden CS, Rudiger SR, et al. An ovine transgenic Huntington’s disease model. Hum Mol Genet 2010;19:1873-82.
91. Huntington’s Disease Sheep Collaborative Research Group, Reid SJ, Patassini S, Handley RR, et al. Further molecular characterisation of the OVT73 transgenic sheep model of Huntington’s disease identifies cortical aggregates. J Huntingtons Dis 2013;2:279-95.
92. Morton AJ, Rudiger SR, Wood NI, et al. Early and progressive circadian abnormalities in Huntington’s disease sheep are unmasked by social environment. Hum Mol Genet 2014;23:3375-83.
93. Yang SH, Cheng PH, Banta H, et al. Towards a transgenic model of Huntington’s disease in a non-human primate. Nature 2008;453:921-4.
94. Snyder BR, Chan AWS. Progress in developing transgenic monkey model for Huntington’s disease. J Neural Transm 2018;125:401-17.
95. Chan AW, Jiang J, Chen Y, et al. Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood. PLoS One 2015;10:e0122335.
96. Yan S, Li S, Li XJ. Use of large animal models to investigate Huntington’s diseases. Cell Regen 2019;8:9-11.
97. Coe CL, Lubach GR. Maternal determinants of gestation length in the rhesus monkey. Trends Dev Biol 2021;14:63-72.
98. Tian CY. China is facing serious experimental monkey shortage during the COVID-19 lockdown. J Med Primatol 2021;50:225-7.
99. Yang D, Wang CE, Zhao B, et al. Expression of Huntington’s disease protein results in apoptotic neurons in the brains of cloned transgenic pigs. Hum Mol Genet 2010;19:3983-94.
100. Yan S, Tu Z, Liu Z, et al. A huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell 2018;173:989-1002.e13.
101. Brignull HR, Moore FE, Tang SJ, Morimoto RI. Polyglutamine proteins at the pathogenic threshold display neuron-specific aggregation in a pan-neuronal Caenorhabditis elegans model. J Neurosci 2006;26:7597-606.
102. Nagai Y, Fujikake N, Ohno K, et al. Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. Hum Mol Genet 2003;12:1253-9.
103. Marsh JL, Walker H, Theisen H, et al. Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila. Hum Mol Genet 2000;9:13-25.
104. Le Bourg E, Lints FA. Hypergravity and aging in Drosophila melanogaster. 4. Climbing activity: 4. Climbing Activity. Gerontology 1992;38:59-64.
105. Chongtham A, Agrawal N. Curcumin modulates cell death and is protective in Huntington’s disease model. Sci Rep 2016;6:18736.
106. Ganetzky B, Flanagan JR. On the relationship between senescence and age-related changes in two wild-type strains of Drosophila melanogaster. Exp Gerontol 1978;13:189-96.
107. Jackson GR, Salecker I, Dong X, et al. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 1998;21:633-42.
108. Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993;118:401-15.
109. Muqit MM, Feany MB. Modelling neurodegenerative diseases in Drosophila: a fruitful approach? Nat Rev Neurosci 2002;3:237-43.
110. Tomasiewicz HG, Flaherty DB, Soria JP, Wood JG. Transgenic zebrafish model of neurodegeneration. J Neurosci Res 2002;70:734-45.
