Mechanisms of transcriptional dysregulation in Huntington's disease

被引：44

作者：

Luthi-Carter, R ^{[1
]}

Cha, JHJ ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA

来源：

CLINICAL NEUROSCIENCE RESEARCH | 2003年 / 3卷 / 03期

关键词：

Huntington's disease; transcription; messenger RNA; expression profiling; huntingtin; polyglutamine disease;

D O I：

10.1016/S1566-2772(03)00059-8

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Recent studies have provided strong evidence for transcription-related deficits in Huntington's disease (HD). These discoveries include consistent changes in steady-state mRNA levels, direct interactions between huntingtin and known transcription factor proteins, sequestration of transcription-related factors into polyglutamine aggregates, and inhibition of enzymes involved in chromatin remodeling. Also, there is increasing evidence that huntingtin itself may be a transcriptional regulator. This review discusses the cumulative body of evidence for transcriptional dysregulation as a mechanism of HD pathogenesis and possible implications for disease progression and treatment. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：165 / 177

页数：13

共 97 条

[1] Huntington's disease progression PET and clinical observations [J].

Andrews, TC ;

Weeks, RA ;

Turjanski, N ;

Gunn, RN ;

Watkins, LHA ;

Sahakian, B ;

Hodges, JR ;

Rosser, AE ;

Wood, NW ;

Brooks, DJ .

BRAIN, 1999, 122 :2353-2363

[2] Striatal neurochemical changes in transgenic models of Huntington's disease [J].

Ariano, MA ;

Aronin, N ;

Difiglia, M ;

Tagle, DA ;

Sibley, DR ;

Leavitt, BR ;

Hayden, MR ;

Levine, MS .

JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 68 (06) :716-729

[3] Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: A detailed cellular in situ hybridization study [J].

Augood, SJ ;

Faull, RLM ;

Love, DR ;

Emson, PC .

NEUROSCIENCE, 1996, 72 (04) :1023-1036

[4] Dopamine D-1 and D-2 receptor gene expression in the striatum in Huntington's disease [J].

Augood, SJ ;

Faull, RLM ;

Emson, PC .

ANNALS OF NEUROLOGY, 1997, 42 (02) :215-221

[5] Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice [J].

Bibb, JA ;

Yan, Z ;

Svenningsson, P ;

Snyder, GL ;

Pieribone, VA ;

Horiuchi, A ;

Nairn, AC ;

Messer, A ;

Greengard, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6809-6814

[6] Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin [J].

Boutell, JM ;

Thomas, P ;

Neal, JW ;

Weston, VJ ;

Duce, J ;

Harper, PS ;

Jones, AL .

HUMAN MOLECULAR GENETICS, 1999, 8 (09) :1647-1655

[7]

Cepeda C, 2003, J NEUROSCI, V23, P961

[8] Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease [J].

Cha, JHJ ;

Frey, AS ;

Alsdorf, SA ;

Kerner, JA ;

Kosinski, CM ;

Mangiarini, L ;

Penney, JB ;

Davies, SW ;

Bates, GP ;

Young, AB .

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1999, 354 (1386) :981-989

[9] Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene [J].

Cha, JHJ ;

Kosinski, CM ;

Kerner, JA ;

Alsdorf, SA ;

Mangiarini, L ;

Davies, SW ;

Penney, JB ;

Bates, GP ;

Young, AB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6480-6485

[10] Transcriptional dysregulation in Huntington's disease [J].

Cha, JHJ .

TRENDS IN NEUROSCIENCES, 2000, 23 (09) :387-392

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