کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4353728 | 1298494 | 2010 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease
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کلمات کلیدی
NMDAQUINN-methyl-d-aspartic acidIDOAP5httAMPA3-HKKynureninesAP7QPRT3-hydroxykynurenine - 3-هیدروکسی ...ROS - ROSKMO - SMEα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid - اسید α-آمینو 3-هیدروکسی-5-متیل-4-ایزوکسول پپونیکkynurenic acid - اسید کینورنیکQuinolinic acid - اسید کینولینیکexcitotoxicity - اکسید سمیتindoleamine-2,3-dioxygenase - ایندولامین-2،3-دیوکسژیگنازHuntington's disease - بیماری هانتینگتونCNS - دستگاه عصبی مرکزیcentral nervous system - سیستم عصبی مرکزیNeuroprotection - محافظت نورونی یا محافظت از عصبkynurenine pathway - مسیر kynurenineMicroglia - میکروگلیاهاHuntingtin - هانتینگتنKYNA - کیاناReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The neurodegenerative disease Huntington's disease (HD) is caused by an expanded polyglutamine (polyQ) tract in the protein huntingtin (htt). Although the gene encoding htt was identified and cloned more than 15 years ago, and in spite of impressive efforts to unravel the mechanism(s) by which mutant htt induces nerve cell death, these studies have so far not led to a good understanding of pathophysiology or an effective therapy. Set against a historical background, we review data supporting the idea that metabolites of the kynurenine pathway (KP) of tryptophan degradation provide a critical link between mutant htt and the pathophysiology of HD. New studies in HD brain and genetic model organisms suggest that the disease may in fact be causally related to early abnormalities in KP metabolism, favoring the formation of two neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, over the related neuroprotective agent kynurenic acid. These findings not only link the excitotoxic hypothesis of HD pathology to an impairment of the KP but also define new drug targets and therefore have direct therapeutic implications. Thus, pharmacological normalization of the imbalance in brain KP metabolism may provide clinical benefits, which could be especially effective in early stages of the disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neurobiology - Volume 90, Issue 2, 9 February 2010, Pages 230-245
Journal: Progress in Neurobiology - Volume 90, Issue 2, 9 February 2010, Pages 230-245
نویسندگان
Robert Schwarcz, Paolo Guidetti, Korrapati V. Sathyasaikumar, Paul J. Muchowski,