کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259094 | 1534630 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Metabolic signatures of Huntington's disease (HD): 1H NMR analysis of the polar metabolome in post-mortem human brain
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کلمات کلیدی
GC-TOF-MSAUROCDSSFDR1H NMR - 1H-NMRAUC - AUCBranched-chain amino acid - آمینو اسید زنجیره ایBCAA - بی سی ای ایAlzheimer's disease - بیماری آلزایمرfMRI - تصویرسازی تشدید مغناطیسی کارکردیfunctional magnetic resonance imaging - تصویرسازی تشدید مغناطیسی کارکردیCNS - دستگاه عصبی مرکزیBBB - سد خونی مغزیblood brain barrier - سد خونی مغزیsodium 2,2-dimethyl-2-silapentane-5-sulfonate - سدیم 2،2-دی متیل-2-سیلپنتان 5-سولفوناتCerebral Spinal Fluid - سیالات مغزی نخاعیcentral nervous system - سیستم عصبی مرکزیCSF - مایع مغزی نخاعیarea under the receiver operating characteristic curve - محدوده تحت منحنی مشخصه عملکرد گیرندهarea under the curve - منطقه تحت منحنیfalse discovery rate - میزان کشف کاذبproton nuclear magnetic resonance - پروتون مغناطیسی رزونانس هسته ای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using 1H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n = 14) and frontal lobe (n = 14) from HD sufferers and controls (n = 28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (p < 0.05; q < 0.3). The metabolite which changed most overall was urea which decreased 3.25-fold in striatum (p < 0.01). Four metabolites were consistently affected in both brain regions. These included the neurotransmitter precursors tyrosine and l-phenylalanine which were significantly depleted by 1.55-1.58-fold and 1.48-1.54-fold in striatum and frontal lobe, respectively (p = 0.02-0.03). They also included l-leucine which was reduced 1.54-1.69-fold (p = 0.04-0.09) and myo-inositol which was increased 1.26-1.37-fold (p < 0.01). Logistic regression analyses performed with MetaboAnalyst demonstrated that data obtained from striatum produced models which were profoundly more sensitive and specific than those produced from frontal lobe. The brain metabolite changes uncovered in this first 1H NMR investigation of human HD offer new insights into the disease pathophysiology. Further investigations of striatal metabolite disturbances are clearly warranted.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 9, September 2016, Pages 1675-1684
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 9, September 2016, Pages 1675-1684
نویسندگان
Stewart F. Graham, Praveen K. Kumar, Trent Bjorndahl, BeomSoo Han, Ali Yilmaz, Eric Sherman, Ray O. Bahado-Singh, David Wishart, David Mann, Brian D. Green,