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Korean J. Vet. Serv. 2021; 44(4): 185-194

Published online December 30, 2021

https://doi.org/10.7853/kjvs.2021.44.4.185

© The Korean Socitety of Veterinary Service

Characterization of binding specificity using GST-conjugated mutant huntingtin epitopes in surface plasmon resonance (SPR)

Hang-Hee Cho 1, Tae Hoon Kim 2, Hong-Duck Kim 3, Jae-Hyeon Cho 1*

1Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea
2Department of Food Science and Biotechnology, Daegu University, Gyungsan 38453, Korea
3Department of Public Health (Division of Environmental Health Science), New York Medical College, Valhalla, NY 10595-1585, USA

Correspondence to : Jae-Hyeon Cho
E-mail: jaehcho@gnu.ac.kr
https://orcid.org/0000-0003-1126-9809

Received: September 3, 2021; Revised: October 29, 2021; Accepted: November 24, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0). which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington’s disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

Keywords Huntington's disease, Mutant huntingtin, Polyglutamine, Surface plasmon resonance

  1. Bano D, Zanetti F, Mende Y, Nicotera P. 2011. Neurodegenerative processes in Huntington’s disease. Cell Death Dis. 10;2(11): e228.
    Pubmed KoreaMed CrossRef
  2. Bhide PG, Day M, Sapp E, Schwarz C, Sheth A, Kim J, Young AB, Penney J, Golden J, Aronin N, M. DiFiglia M. 1996. Expression of normal and mutant huntingtin in the developing brain. J Neurosci. 16: 5523-35.
    Pubmed KoreaMed CrossRef
  3. Burrus CJ, McKinstry SU, Kim N, Ilcim Ozlu M, Santoki AV, Fang FY, Ma A, Karadeniz YB, Worthington AK, Dragatsis I, Zeitlin S, Yin HH, Eroglu C. 2020. Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival. Cell Rep. 30(3): 642-657.
    Pubmed KoreaMed CrossRef
  4. Busch A, Engemann S, Lurz R, Okazawa H, Lehrach H, Wanker EE. 2003. Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington’s disease. J Biol Chem. 278: 41452-61.
    Pubmed CrossRef
  5. Cooper JK, Schilling G, Peters MF, Herring WJ, Sharp AH, Kaminsky Z, Masone J, Khan FA, Delanoy M, Borchelt DR, Dawson VL, Dawson TM, Ross CA. 1998. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet. 7: 783-90.
    Pubmed CrossRef
  6. Dabrowska M, Juzwa W, Krzyzosiak WJ, Olejniczak M. 2018. Precise Excision of the CAG Tract from the Huntingtin Gene by Cas9 Nickases. Front Neurosci. 12: 75.
    Pubmed KoreaMed CrossRef
  7. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 277: 1990-3.
    Pubmed CrossRef
  8. Dunah AW, Jeong H, Griffin A, Kim YM, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D. 2002. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington’s disease. Science. 296: 2238-43.
    Pubmed CrossRef
  9. Hackam AS, Singaraja R, Wellington CL, Metzler M, McCutcheon K, Zhang T, Kalchman M, Hayden MR. 1998. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol. 141: 1097-105.
    Pubmed KoreaMed CrossRef
  10. Hackam AS, Singaraja R, Zhang T, Gan, L. Hayden MR. 1999. In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington’s disease. Hum Mol Genet. 8: 25-33.
    Pubmed CrossRef
  11. Jana NR, Tanaka M, Wang G, Nukina N. 2000. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity, Hum Mol Genet. 9: 2009-18.
    Pubmed CrossRef
  12. Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI. 2002. Polyglutamine protein aggregates are dynamic. Nat Cell Biol. 4: 826-31.
    Pubmed CrossRef
  13. Koshy BT, Zoghbi HY. 1997. The CAG/polyglutamine tract diseases: gene products and molecular pathogenesis. Brain Pathol. 7: 927-42.
    Pubmed KoreaMed CrossRef
  14. Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ. 2002. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol. 22: 1277-87.
    Pubmed KoreaMed CrossRef
  15. Li SH, Li XJ. 1998. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum Mol Genet. 7: 777-82.
    Pubmed CrossRef
  16. Li SH, Li XJ. 2004. Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends in Genetics. 20: 146-154.
    Pubmed CrossRef
  17. Lunkes A, Trottier Y, Fagart J, Schultz P, Zeder-Lutz G, Moras D, Mandel JL. 1999. Properties of polyglutamine expansion in vitro and in a cellular model for Huntington’s disease. Philos Trans R Soc Lond B Biol Sci. 354: 1013-1019.
    Pubmed KoreaMed CrossRef
  18. Marquette A, Aisenbrey C, Bechinger B. 2021. Membrane Interactions Accelerate the Self-Aggregation of Huntingtin Exon 1 Fragments in a Polyglutamine Length-Dependent Manner. Int J Mol Sci. 22(13): 6725.
    Pubmed KoreaMed CrossRef
  19. Martin JB, Gusella J. 1986. Huntington’s disease. Pathogenesis and management. N Engl J Med. 315; 1267-76.
    Pubmed CrossRef
  20. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, McCutcheon K, Singaraja RKazemi-Esfarjani P, Devon R, Kim SU, Bredesen DE, Tufaro F, Hayden MR. 1998. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet. 18: 150-4.
    Pubmed CrossRef
  21. Moulder KL, Onodera O, Burke JR, Strittmatter WJ, Jr. Johnson EM. 1999. Generation of neuronal intranuclear inclusions by polyglutamine-GFP: analysis of inclusion clearance and toxicity as a function of polyglutamine length. J Neurosci. 19: 705-15.
    Pubmed KoreaMed CrossRef
  22. Narain Y, Wyttenbach A, Rankin J, Furlong RA, Rubinsztein DC. 1999. A molecular investigation of true dominance in Huntington’s disease. J Med Genet. 36: 739-46.
    Pubmed KoreaMed CrossRef
  23. Preisinger E, Jordan BM, Kazantsev A, Housman D. 1999. Evidence for a recruitment and sequestration mechanism in Huntington’s disease. Philos Trans R Soc Lond B Biol Sci. 354: 1029-34.
    Pubmed KoreaMed CrossRef
  24. Reddy PH, Williams M, Tagle DA. 1999. Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci. 22: 248-55.
    CrossRef
  25. Rigamonti D, Bauer JH, De-Fraja C, Conti L, Sipione S, Sciorati C, Clementi E, Hackam A, Hayden MR, Li Y, Cooper JK, Ross CA, Govoni S, Vincenz C, Cattaneo E. 2000. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci. 20: 3705-13.
    Pubmed KoreaMed CrossRef
  26. Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman JJ, Chotai K, Connarty M, Crauford D, Curtis A, Curtis D, Davidson MJ, Differ AM, Dode C, Dodge A, Frontali M, Ranen NG, Stine OC, Sherr M, Abbott MH, Franz ML, Graham CA, Harper PS, Hedreen JC, Jackson A, Kaplan JC, Losekoot M, MacMillan JC, Morrison P, Trottier Y, Novelletto A, Simpson SA, Theilmann J, Whittaker JL, Folstein SE, Ross CA, Hayden MR. 1996. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet. 59: 16-22.
  27. Sharp AH, Love SJ, Schilling G, Li SH, Li XJ, Bao J, Wagster MV, Kotzuk JA. Steiner JP, Lo A, Hedreen J, Sisodia S, Snyder SH, Dawson TM, Ryugo DK, Ross CA. 1995. Widespread expression of Huntington’s disease gene (IT15) protein product. Neuron. 14: 1065-74.
    CrossRef
  28. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson Jr EP. 1985. Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol. 44; 559-77.
    Pubmed CrossRef
  29. Walker FO, 2007. Huntington’s disease. Lancet. 369 (9557): 218-28.
    CrossRef
  30. Yang H, Yang S, Jing L, Huang L, Chen L, Zhao X, Yang W, Pan Y, Yin P, Qin ZS, Tang B, Li S, Li XJ. 2020. Truncation of mutant huntingtin in knock-in mice demonstrates exon1 huntingtin is akey pathogenic form. Nat Commun. 11(1): 2582.
    Pubmed KoreaMed CrossRef
  31. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattane E. 2003. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 35: 76-83.
    Pubmed CrossRef

Article

Original Article

Korean J. Vet. Serv. 2021; 44(4): 185-194

Published online December 30, 2021 https://doi.org/10.7853/kjvs.2021.44.4.185

Copyright © The Korean Socitety of Veterinary Service.

Characterization of binding specificity using GST-conjugated mutant huntingtin epitopes in surface plasmon resonance (SPR)

Hang-Hee Cho 1, Tae Hoon Kim 2, Hong-Duck Kim 3, Jae-Hyeon Cho 1*

1Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea
2Department of Food Science and Biotechnology, Daegu University, Gyungsan 38453, Korea
3Department of Public Health (Division of Environmental Health Science), New York Medical College, Valhalla, NY 10595-1585, USA

Correspondence to:Jae-Hyeon Cho
E-mail: jaehcho@gnu.ac.kr
https://orcid.org/0000-0003-1126-9809

Received: September 3, 2021; Revised: October 29, 2021; Accepted: November 24, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0). which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington’s disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

Keywords: Huntington's disease, Mutant huntingtin, Polyglutamine, Surface plasmon resonance

References

  1. Bano D, Zanetti F, Mende Y, Nicotera P. 2011. Neurodegenerative processes in Huntington’s disease. Cell Death Dis. 10;2(11): e228.
    Pubmed KoreaMed CrossRef
  2. Bhide PG, Day M, Sapp E, Schwarz C, Sheth A, Kim J, Young AB, Penney J, Golden J, Aronin N, M. DiFiglia M. 1996. Expression of normal and mutant huntingtin in the developing brain. J Neurosci. 16: 5523-35.
    Pubmed KoreaMed CrossRef
  3. Burrus CJ, McKinstry SU, Kim N, Ilcim Ozlu M, Santoki AV, Fang FY, Ma A, Karadeniz YB, Worthington AK, Dragatsis I, Zeitlin S, Yin HH, Eroglu C. 2020. Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival. Cell Rep. 30(3): 642-657.
    Pubmed KoreaMed CrossRef
  4. Busch A, Engemann S, Lurz R, Okazawa H, Lehrach H, Wanker EE. 2003. Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington’s disease. J Biol Chem. 278: 41452-61.
    Pubmed CrossRef
  5. Cooper JK, Schilling G, Peters MF, Herring WJ, Sharp AH, Kaminsky Z, Masone J, Khan FA, Delanoy M, Borchelt DR, Dawson VL, Dawson TM, Ross CA. 1998. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet. 7: 783-90.
    Pubmed CrossRef
  6. Dabrowska M, Juzwa W, Krzyzosiak WJ, Olejniczak M. 2018. Precise Excision of the CAG Tract from the Huntingtin Gene by Cas9 Nickases. Front Neurosci. 12: 75.
    Pubmed KoreaMed CrossRef
  7. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 277: 1990-3.
    Pubmed CrossRef
  8. Dunah AW, Jeong H, Griffin A, Kim YM, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D. 2002. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington’s disease. Science. 296: 2238-43.
    Pubmed CrossRef
  9. Hackam AS, Singaraja R, Wellington CL, Metzler M, McCutcheon K, Zhang T, Kalchman M, Hayden MR. 1998. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol. 141: 1097-105.
    Pubmed KoreaMed CrossRef
  10. Hackam AS, Singaraja R, Zhang T, Gan, L. Hayden MR. 1999. In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington’s disease. Hum Mol Genet. 8: 25-33.
    Pubmed CrossRef
  11. Jana NR, Tanaka M, Wang G, Nukina N. 2000. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity, Hum Mol Genet. 9: 2009-18.
    Pubmed CrossRef
  12. Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI. 2002. Polyglutamine protein aggregates are dynamic. Nat Cell Biol. 4: 826-31.
    Pubmed CrossRef
  13. Koshy BT, Zoghbi HY. 1997. The CAG/polyglutamine tract diseases: gene products and molecular pathogenesis. Brain Pathol. 7: 927-42.
    Pubmed KoreaMed CrossRef
  14. Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ. 2002. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol. 22: 1277-87.
    Pubmed KoreaMed CrossRef
  15. Li SH, Li XJ. 1998. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum Mol Genet. 7: 777-82.
    Pubmed CrossRef
  16. Li SH, Li XJ. 2004. Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends in Genetics. 20: 146-154.
    Pubmed CrossRef
  17. Lunkes A, Trottier Y, Fagart J, Schultz P, Zeder-Lutz G, Moras D, Mandel JL. 1999. Properties of polyglutamine expansion in vitro and in a cellular model for Huntington’s disease. Philos Trans R Soc Lond B Biol Sci. 354: 1013-1019.
    Pubmed KoreaMed CrossRef
  18. Marquette A, Aisenbrey C, Bechinger B. 2021. Membrane Interactions Accelerate the Self-Aggregation of Huntingtin Exon 1 Fragments in a Polyglutamine Length-Dependent Manner. Int J Mol Sci. 22(13): 6725.
    Pubmed KoreaMed CrossRef
  19. Martin JB, Gusella J. 1986. Huntington’s disease. Pathogenesis and management. N Engl J Med. 315; 1267-76.
    Pubmed CrossRef
  20. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, McCutcheon K, Singaraja RKazemi-Esfarjani P, Devon R, Kim SU, Bredesen DE, Tufaro F, Hayden MR. 1998. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet. 18: 150-4.
    Pubmed CrossRef
  21. Moulder KL, Onodera O, Burke JR, Strittmatter WJ, Jr. Johnson EM. 1999. Generation of neuronal intranuclear inclusions by polyglutamine-GFP: analysis of inclusion clearance and toxicity as a function of polyglutamine length. J Neurosci. 19: 705-15.
    Pubmed KoreaMed CrossRef
  22. Narain Y, Wyttenbach A, Rankin J, Furlong RA, Rubinsztein DC. 1999. A molecular investigation of true dominance in Huntington’s disease. J Med Genet. 36: 739-46.
    Pubmed KoreaMed CrossRef
  23. Preisinger E, Jordan BM, Kazantsev A, Housman D. 1999. Evidence for a recruitment and sequestration mechanism in Huntington’s disease. Philos Trans R Soc Lond B Biol Sci. 354: 1029-34.
    Pubmed KoreaMed CrossRef
  24. Reddy PH, Williams M, Tagle DA. 1999. Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci. 22: 248-55.
    CrossRef
  25. Rigamonti D, Bauer JH, De-Fraja C, Conti L, Sipione S, Sciorati C, Clementi E, Hackam A, Hayden MR, Li Y, Cooper JK, Ross CA, Govoni S, Vincenz C, Cattaneo E. 2000. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci. 20: 3705-13.
    Pubmed KoreaMed CrossRef
  26. Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman JJ, Chotai K, Connarty M, Crauford D, Curtis A, Curtis D, Davidson MJ, Differ AM, Dode C, Dodge A, Frontali M, Ranen NG, Stine OC, Sherr M, Abbott MH, Franz ML, Graham CA, Harper PS, Hedreen JC, Jackson A, Kaplan JC, Losekoot M, MacMillan JC, Morrison P, Trottier Y, Novelletto A, Simpson SA, Theilmann J, Whittaker JL, Folstein SE, Ross CA, Hayden MR. 1996. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet. 59: 16-22.
  27. Sharp AH, Love SJ, Schilling G, Li SH, Li XJ, Bao J, Wagster MV, Kotzuk JA. Steiner JP, Lo A, Hedreen J, Sisodia S, Snyder SH, Dawson TM, Ryugo DK, Ross CA. 1995. Widespread expression of Huntington’s disease gene (IT15) protein product. Neuron. 14: 1065-74.
    CrossRef
  28. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson Jr EP. 1985. Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol. 44; 559-77.
    Pubmed CrossRef
  29. Walker FO, 2007. Huntington’s disease. Lancet. 369 (9557): 218-28.
    CrossRef
  30. World Health Organization. 2019.disorders. https://www.who.int/news-room/fact-sheets/detail/mental-disorders.
  31. Yang H, Yang S, Jing L, Huang L, Chen L, Zhao X, Yang W, Pan Y, Yin P, Qin ZS, Tang B, Li S, Li XJ. 2020. Truncation of mutant huntingtin in knock-in mice demonstrates exon1 huntingtin is akey pathogenic form. Nat Commun. 11(1): 2582.
    Pubmed KoreaMed CrossRef
  32. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattane E. 2003. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 35: 76-83.
    Pubmed CrossRef
KJVS
Jun 30, 2022 Vol.45 No.2, pp. 101~99

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