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Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease
Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the HTT gene. HD usually manifests in mid-life with loss of GABAergic projection neurons from the striatum accompanied by progressive atrophy of the putamen followed by other brain regions, but li...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630497/ https://www.ncbi.nlm.nih.gov/pubmed/31212603 http://dx.doi.org/10.3390/metabo9060113 |
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author | Patassini, Stefano Begley, Paul Xu, Jingshu Church, Stephanie J. Kureishy, Nina Reid, Suzanne J. Waldvogel, Henry J. Faull, Richard L. M. Snell, Russell G. Unwin, Richard D. Cooper, Garth J. S. |
author_facet | Patassini, Stefano Begley, Paul Xu, Jingshu Church, Stephanie J. Kureishy, Nina Reid, Suzanne J. Waldvogel, Henry J. Faull, Richard L. M. Snell, Russell G. Unwin, Richard D. Cooper, Garth J. S. |
author_sort | Patassini, Stefano |
collection | PubMed |
description | Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the HTT gene. HD usually manifests in mid-life with loss of GABAergic projection neurons from the striatum accompanied by progressive atrophy of the putamen followed by other brain regions, but linkages between the genetics and neurodegeneration are not understood. We measured metabolic perturbations in HD-human brain in a case-control study, identifying pervasive lowering of vitamin B5, the obligatory precursor of coenzyme A (CoA) that is essential for normal intermediary metabolism. Cerebral pantothenate deficiency is a newly-identified metabolic defect in human HD that could potentially: (i) impair neuronal CoA biosynthesis; (ii) stimulate polyol-pathway activity; (iii) impair glycolysis and tricarboxylic acid cycle activity; and (iv) modify brain-urea metabolism. Pantothenate deficiency could lead to neurodegeneration/dementia in HD that might be preventable by treatment with vitamin B5. |
format | Online Article Text |
id | pubmed-6630497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66304972019-08-19 Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease Patassini, Stefano Begley, Paul Xu, Jingshu Church, Stephanie J. Kureishy, Nina Reid, Suzanne J. Waldvogel, Henry J. Faull, Richard L. M. Snell, Russell G. Unwin, Richard D. Cooper, Garth J. S. Metabolites Article Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the HTT gene. HD usually manifests in mid-life with loss of GABAergic projection neurons from the striatum accompanied by progressive atrophy of the putamen followed by other brain regions, but linkages between the genetics and neurodegeneration are not understood. We measured metabolic perturbations in HD-human brain in a case-control study, identifying pervasive lowering of vitamin B5, the obligatory precursor of coenzyme A (CoA) that is essential for normal intermediary metabolism. Cerebral pantothenate deficiency is a newly-identified metabolic defect in human HD that could potentially: (i) impair neuronal CoA biosynthesis; (ii) stimulate polyol-pathway activity; (iii) impair glycolysis and tricarboxylic acid cycle activity; and (iv) modify brain-urea metabolism. Pantothenate deficiency could lead to neurodegeneration/dementia in HD that might be preventable by treatment with vitamin B5. MDPI 2019-06-11 /pmc/articles/PMC6630497/ /pubmed/31212603 http://dx.doi.org/10.3390/metabo9060113 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Patassini, Stefano Begley, Paul Xu, Jingshu Church, Stephanie J. Kureishy, Nina Reid, Suzanne J. Waldvogel, Henry J. Faull, Richard L. M. Snell, Russell G. Unwin, Richard D. Cooper, Garth J. S. Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title | Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title_full | Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title_fullStr | Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title_full_unstemmed | Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title_short | Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease |
title_sort | cerebral vitamin b5 (d-pantothenic acid) deficiency as a potential cause of metabolic perturbation and neurodegeneration in huntington’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630497/ https://www.ncbi.nlm.nih.gov/pubmed/31212603 http://dx.doi.org/10.3390/metabo9060113 |
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