دورية أكاديمية
Role of Dynein Axonemal Heavy Chain 6 Gene Expression as a Possible Biomarker for Huntington's Disease: a Translational Study.
العنوان: | Role of Dynein Axonemal Heavy Chain 6 Gene Expression as a Possible Biomarker for Huntington's Disease: a Translational Study. |
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المؤلفون: | Areal LB; Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitória, ES, Brazil.; Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Pereira LP; Graduate Program in Biochemistry and Pharmacology, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil., Ribeiro FM; Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Olmo IG; Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Muniz MR; Department of Clinical Medicine, Health Science Center, Federal University of Espírito Santo, Vitória, Brazil., do Carmo Rodrigues M; Department of Clinical Medicine, Health Science Center, Federal University of Espírito Santo, Vitória, Brazil., Costa PF; Department of Physiotherapy, School of Sciences, Santa Casa de Misericordia de Vitoria, Vitória, ES, Brazil., Martins-Silva C; Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitória, ES, Brazil.; Graduate Program in Biochemistry and Pharmacology, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil., Ferguson SSG; Department of Cellular and Molecular Medicine, Brain and Mind Research Institute and Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada., Guimarães DAM; Graduate Program in Biochemistry and Pharmacology, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil., Pires RGW; Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitória, ES, Brazil. rita.pires@ufes.br.; Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. rita.pires@ufes.br.; Graduate Program in Biochemistry and Pharmacology, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil. rita.pires@ufes.br.; Department of Physiological Sciences, Health Science Center, Federal University of Espírito Santo, Marechal Campos Avenue, 1468, Vitória, ES, 29043-910, Brazil. rita.pires@ufes.br. |
المصدر: | Journal of molecular neuroscience : MN [J Mol Neurosci] 2017 Dec; Vol. 63 (3-4), pp. 342-348. Date of Electronic Publication: 2017 Oct 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Humana Press Country of Publication: United States NLM ID: 9002991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1166 (Electronic) Linking ISSN: 08958696 NLM ISO Abbreviation: J Mol Neurosci Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Totowa, NJ : Humana Press Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989- |
مواضيع طبية MeSH: | Dyneins/*blood , Huntington Disease/*blood, Animals ; Biomarkers/blood ; Case-Control Studies ; Down-Regulation ; Dyneins/genetics ; Dyneins/metabolism ; Humans ; Huntingtin Protein ; Huntington Disease/genetics ; Huntington Disease/pathology ; Mice ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Translational Research, Biomedical |
مستخلص: | Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive deficits, and psychiatric symptoms. The primary genetic cause is an expansion of cytosine adenine guanine (CAG) nucleotides of the huntingtin gene, which codes an important protein involved with neuronal signaling. The severity of HD correlates with the number of CAG repeats and individuals with longer expansions have an earlier onset and more severe symptoms. A microarray study conducted by our research group showed alteration in DNAH6 gene (encoding dynein axonemal heavy chain 6). DNAH6 belongs to dynein family, whose members are constituents of the microtubule-associated motor proteins and is downregulated in the striatum of a HD mouse model (knockin Hdh Q111/Q111 ). In this manner, our goal was to confirm these downregulations in the mouse model and verify if the same alteration in the axonemal DNAH6 gene expression is observed in blood samples of HD patients. Blood samples were collected from 17 patients with clinical diagnosis of HD and 12 healthy individuals and RNA extracted for qPCR analysis. Microarray data were confirmed by qPCR in knockin Hdh Q111/Q111 , and DNAH6 was severely decreased in those mice, as compared to control mice (Hdh Q20/Q20 ). Notably, decreased expression of DNAH6 gene was also observed in HD patients when compared to control group and negatively correlates with the CAG expansion. Although further studies are necessary to underlie the molecular mechanisms of dynein-htt interaction, this data highlights DNAH6 as a potential new blood marker for HD. |
References: | Clin Genet. 2004 Apr;65(4):267-77. (PMID: 15025718) Neurobiol Dis. 2013 Oct;58:220-30. (PMID: 23742762) Nucleic Acids Res. 2002 Aug 15;30(16):e83. (PMID: 12177311) Am J Hum Genet. 1997 May;60(5):1202-10. (PMID: 9150168) Cell Mol Neurobiol. 2013 Apr;33(3):327-35. (PMID: 23263842) J Vis Exp. 2009 May 29;(27):null. (PMID: 19488029) Nat Rev Mol Cell Biol. 2013 Nov;14(11):713-26. (PMID: 24064538) Neuron. 1995 May;14 (5):1075-81. (PMID: 7748555) Cell. 1993 Mar 26;72(6):971-83. (PMID: 8458085) J Neuropathol Exp Neurol. 1998 May;57(5):369-84. (PMID: 9596408) Arq Neuropsiquiatr. 2000 Mar;58(1):11-7. (PMID: 10770860) Br J Pharmacol. 2013 Jun;169(4):909-21. (PMID: 23489026) Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10045-50. (PMID: 17548833) Int J Neuropsychopharmacol. 2009 Feb;12(1):45-60. (PMID: 18593507) Nat Rev Mol Cell Biol. 2009 Dec;10 (12 ):854-65. (PMID: 19935668) Cell Death Differ. 2015 Sep;22(9):1413-24. (PMID: 26160070) Nat Genet. 1993 Aug;4(4):387-92. (PMID: 8401587) Hum Mol Genet. 2014 Apr 15;23(8):2030-42. (PMID: 24282028) Nat Rev Neurol. 2009 Jun;5(6):311-22. (PMID: 19498435) Hum Mol Genet. 2002 May 1;11(9):1107-17. (PMID: 11978769) Brain Res. 2004 Sep 3;1019(1-2):246-54. (PMID: 15306259) Mol Neurobiol. 2011 Feb;43(1):1-11. (PMID: 21153060) J Clin Invest. 2011 Nov;121(11):4372-82. (PMID: 21985783) Hum Mol Genet. 1993 Oct;2(10):1547-9. (PMID: 8268907) Proteomics Clin Appl. 2015 Feb;9(1-2):147-58. (PMID: 25290828) J Cell Biol. 2008 Sep 8;182(5):951-62. (PMID: 18779373) |
فهرسة مساهمة: | Keywords: Dynein heavy chain 6; Gene expression; Huntington’s disease; Microarray |
المشرفين على المادة: | 0 (Biomarkers) 0 (Htt protein, mouse) 0 (Huntingtin Protein) 0 (Nerve Tissue Proteins) 0 (Nuclear Proteins) EC 3.6.4.2 (Dyneins) |
تواريخ الأحداث: | Date Created: 20171012 Date Completed: 20180720 Latest Revision: 20211204 |
رمز التحديث: | 20240628 |
DOI: | 10.1007/s12031-017-0984-z |
PMID: | 29019003 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1559-1166 |
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DOI: | 10.1007/s12031-017-0984-z |