دورية أكاديمية
Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease.
| العنوان: | Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease. |
|---|---|
| المؤلفون: | Pfalzer AC; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Shiino S; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Silverman J; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Codreanu SG; Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA., Sherrod SD; Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA., McLean JA; Department of Chemistry and Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA., Claassen DO; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. |
| المصدر: | Journal of Huntington's disease [J Huntingtons Dis] 2024; Vol. 13 (1), pp. 103-111. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: IOS Press Country of Publication: Netherlands NLM ID: 101589965 Publication Model: Print Cited Medium: Internet ISSN: 1879-6400 (Electronic) Linking ISSN: 18796397 NLM ISO Abbreviation: J Huntingtons Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, The Netherlands : IOS Press |
| مواضيع طبية MeSH: | Huntington Disease*/genetics, Animals ; Humans ; Urea/metabolism ; Huntingtin Protein/genetics ; Huntingtin Protein/metabolism ; Disease Progression |
| مستخلص: | Background: Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown. Objective: To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD. Methods: We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls. Results: Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine. Conclusions: Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism. |
| References: | Cells. 2021 May 13;10(5):. (PMID: 34068340) Mov Disord. 2021 May;36(5):1259-1264. (PMID: 33471951) Mol Neurodegener. 2021 Jan 23;16(1):4. (PMID: 33485385) Int J Tryptophan Res. 2022 May 26;15:11786469221102093. (PMID: 35651666) Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):161-6. (PMID: 26522227) Int J Mol Sci. 2021 Oct 15;22(20):. (PMID: 34681773) J Neuroinflammation. 2016 Dec 12;13(1):306. (PMID: 27955696) J Neurochem. 2021 Jul;158(2):539-553. (PMID: 33797782) Elife. 2021 Jan 08;10:. (PMID: 33416496) Neurology. 2017 Dec 12;89(24):2495-2502. (PMID: 29142089) Hum Mol Genet. 2007 Mar 1;16(5):483-98. (PMID: 17213233) Data Brief. 2020 Jun 03;31:105811. (PMID: 32566710) Ther Drug Monit. 2005 Dec;27(6):747-51. (PMID: 16404815) Biol Trace Elem Res. 2013 Feb;151(2):159-70. (PMID: 23225075) Sci Rep. 2020 Nov 24;10(1):20490. (PMID: 33235276) Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000588. (PMID: 27148576) J Clin Invest. 2013 Sep;123(9):4076-88. (PMID: 23985564) Ageing Res Rev. 2020 Nov;63:101152. (PMID: 32846222) Biomicrofluidics. 2018 May 07;12(3):034102. (PMID: 29774083) Sci Rep. 2022 Jun 20;12(1):10373. (PMID: 35725749) Cell Res. 2022 May;32(5):477-490. (PMID: 35105939) Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1596-1604. (PMID: 28213125) J Am Soc Mass Spectrom. 2016 Dec;27(12):1897-1905. (PMID: 27624161) Nucleic Acids Res. 2013 Jan;41(Database issue):D801-7. (PMID: 23161693) Cell. 1993 Mar 26;72(6):971-83. (PMID: 8458085) Brain. 1996 Dec;119 ( Pt 6):2085-95. (PMID: 9010012) Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11293-E11302. (PMID: 29229845) Curr Protoc Bioinformatics. 2019 Dec;68(1):e86. (PMID: 31756036) |
| معلومات مُعتمدة: | R03 NS125243 United States NS NINDS NIH HHS; UL1 TR002243 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: Huntington’s disease; cerebrospinal fluid; metabolism; neurodegeneration; urea |
| المشرفين على المادة: | 8W8T17847W (Urea) 0 (Huntingtin Protein) |
| تواريخ الأحداث: | Date Created: 20240310 Date Completed: 20240401 Latest Revision: 20240714 |
| رمز التحديث: | 20240714 |
| مُعرف محوري في PubMed: | PMC11238568 |
| DOI: | 10.3233/JHD-231511 |
| PMID: | 38461512 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1879-6400 |
|---|---|
| DOI: | 10.3233/JHD-231511 |