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. |
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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. |
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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 |
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DOI: | 10.3233/JHD-231511 |