Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s DiseaseCitation formats

  • External authors:
  • Stefano Patassini
  • Paul Begley
  • Jingshu Xu
  • Stephanie Church
  • Nina Kureishy
  • Suzanne J Reid
  • Henry J. Waldvogel
  • Richard L. M. Faull
  • Russell G Snell

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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; Kureishy, Nina; Reid, Suzanne J; Waldvogel, Henry J. ; Faull, Richard L. M. ; Snell, Russell G; Unwin, Richard; Cooper, Garth JS.

In: Metabolites, 2019.

Research output: Contribution to journalArticle

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Author

Patassini, Stefano ; Begley, Paul ; Xu, Jingshu ; Church, Stephanie ; Kureishy, Nina ; Reid, Suzanne J ; Waldvogel, Henry J. ; Faull, Richard L. M. ; Snell, Russell G ; Unwin, Richard ; Cooper, Garth JS. / Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease. In: Metabolites. 2019.

Bibtex

@article{d2922d7f3c184730837ac8afcb10dff8,
title = "Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease",
abstract = "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.",
keywords = "Huntington's disease, neurodegeneration, vitamin B5, acetyl-coenzyme A, brain energy metabolism, acetylcholine biosynthesis, metabolomics, bioinformatics, data visualisation, data analytics",
author = "Stefano Patassini and Paul Begley and Jingshu Xu and Stephanie Church and Nina Kureishy and Reid, {Suzanne J} and Waldvogel, {Henry J.} and Faull, {Richard L. M.} and Snell, {Russell G} and Richard Unwin and Cooper, {Garth JS}",
year = "2019",
doi = "10.3390/metabo9060113",
language = "English",
journal = "Metabolites",
issn = "2218-1989",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

}

RIS

TY - JOUR

T1 - Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease

AU - Patassini, Stefano

AU - Begley, Paul

AU - Xu, Jingshu

AU - Church, Stephanie

AU - Kureishy, Nina

AU - Reid, Suzanne J

AU - Waldvogel, Henry J.

AU - Faull, Richard L. M.

AU - Snell, Russell G

AU - Unwin, Richard

AU - Cooper, Garth JS

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Huntington's disease

KW - neurodegeneration

KW - vitamin B5

KW - acetyl-coenzyme A

KW - brain energy metabolism

KW - acetylcholine biosynthesis

KW - metabolomics

KW - bioinformatics

KW - data visualisation

KW - data analytics

U2 - 10.3390/metabo9060113

DO - 10.3390/metabo9060113

M3 - Article

JO - Metabolites

JF - Metabolites

SN - 2218-1989

ER -