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

被引：54

作者：

Patassini, Stefano ^{[1
,2
,3
]}

Begley, Paul ^{[1
]}

Xu, Jingshu ^{[1
,4
]}

Church, Stephanie J. ^{[1
]}

Kureishy, Nina ^{[1
]}

Reid, Suzanne J. ^{[2
,5
]}

Waldvogel, Henry J. ^{[5
]}

Faull, Richard L. M. ^{[5
]}

Snell, Russell G. ^{[2
,5
]}

Unwin, Richard D. ^{[1
]}

Cooper, Garth J. S. ^{[1
,2
,4
,6
]}

机构：

[1] Univ Manchester, Fac Biol, Sch Med Sci, Div Cardiovasc Sci,Ctr Adv Discovery & Expt Thera, Manchester M19 9NT, Lancs, England

[2] Univ Auckland, Fac Sci, Sch Biol Sci, Auckland 1142, New Zealand

[3] Cambridge Sci Pk, Owlstone Med, Cambridge CB4 0GJ, England

[4] Univ Manchester, Manchester Canc Res Ctr Bldg, Manchester M20 4GJ, Lancs, England

[5] Univ Auckland, Fac Med & Hlth Sci, Ctr Brain Res, Dept Anat & Med Imaging, Auckland 1142, New Zealand

[6] Univ Auckland, Maurice Wilkins Ctr Mol Biodiscovery, Auckland 1142, New Zealand

来源：

METABOLITES | 2019年 / 9卷 / 06期

关键词：

Huntington's disease; neurodegeneration; vitamin B5; acetyl-coenzyme A; brain energy metabolism; acetylcholine biosynthesis; metabolomics; bioinformatics; data visualisation; data analytics; A BIOSYNTHETIC-PATHWAY; HUMAN BRAIN; TRINUCLEOTIDE REPEAT; ALZHEIMERS-DISEASE; GAS-CHROMATOGRAPHY; BASAL GANGLIA; TRANSPORTER; CYCLE; ORGANIZATION; PREMANIFEST;

D O I：

10.3390/metabo9060113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：21

共 86 条

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