Huntington's disease: Translating a CAG repeat into a pathogenic mechanism

被引：81

作者：

MacDonald, ME

Gusella, JF

机构：

[1] Molecular Neurogenetics Unit, Building 149, Massachusetts General Hospital East, Charlestown

来源：

CURRENT OPINION IN NEUROBIOLOGY | 1996年 / 6卷 / 05期

关键词：

D O I：

10.1016/S0959-4388(96)80097-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The specific pattern of neuronal cell death in Huntington's disease (HD) is triggered by an abnormal version of the huntingtin protein, which is produced by translation of the HD gene defect, an expanded CAG repeat in a novel 4p16.3 gene. The extended amino-terminal polyglutamine segment may act via the protein's inherent activity, increasing ii or decreasing it in a graded fashion, or, alternatively, it may confer the ability to interact with a completely different set of cellular pathways, focusing attention on the HD protein's normal and abnormal physiological functions.

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页码：638 / 643

页数：6

相关论文

共 45 条

[1] ALTERNATIVE EXCITOTOXIC HYPOTHESES [J].

ALBIN, RL ;

GREENAMYRE, JT .

NEUROLOGY, 1992, 42 (04) :733-738

[2] STRUCTURE AND EXPRESSION OF THE HUNTINGTONS-DISEASE GENE - EVIDENCE AGAINST SIMPLE INACTIVATION DUE TO AN EXPANDED CAG REPEAT [J].

AMBROSE, CM ;

DUYAO, MP ;

BARNES, G ;

BATES, GP ;

LIN, CS ;

SRINIDHI, J ;

BAXENDALE, S ;

HUMMERICH, H ;

LEHRACH, H ;

ALTHERR, M ;

WASMUTH, J ;

BUCKLER, A ;

CHURCH, D ;

HOUSMAN, D ;

BERKS, M ;

MICKLEM, G ;

DURBIN, R ;

DODGE, A ;

READ, A ;

GUSELLA, J ;

MACDONALD, ME .

SOMATIC CELL AND MOLECULAR GENETICS, 1994, 20 (01) :27-38

[3]

ANDREW SE, 1994, AM J HUM GENET, V54, P852

[4] CAG EXPANSION AFFECTS THE EXPRESSION OF MUTANT HUNTINGTIN IN THE HUNTINGTONS-DISEASE BRAIN [J].

ARONIN, N ;

CHASE, K ;

YOUNG, C ;

SAPP, E ;

SCHWARZ, C ;

MATTA, N ;

KORNREICH, R ;

LANDWEHRMEYER, B ;

BIRD, E ;

BEAL, MF ;

VONSATTEL, JP ;

SMITH, T ;

CARRAWAY, R ;

BOYCE, FM ;

YOUNG, AB ;

PENNEY, JB ;

DIFIGLIA, M .

NEURON, 1995, 15 (05) :1193-1201

[5] Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin [J].

Bao, J ;

Sharp, AH ;

Wagster, MV ;

Becher, M ;

Schilling, G ;

Ross, CA ;

Dawson, VL ;

Dawson, TM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :5037-5042

[6] MOUSE HUNTINGTONS-DISEASE GENE HOMOLOG (HDH) [J].

BARNES, GT ;

DUYAO, MP ;

AMBROSE, CM ;

MCNEIL, S ;

PERSICHETTI, F ;

SRINIDHI, J ;

GUSELLA, JF ;

MACDONALD, ME .

SOMATIC CELL AND MOLECULAR GENETICS, 1994, 20 (02) :87-97

[7] COMPARATIVE SEQUENCE-ANALYSIS OF THE HUMAN AND PUFFERFISH HUNTINGTONS-DISEASE GENES [J].

BAXENDALE, S ;

ABDULLA, S ;

ELGAR, G ;

BUCK, D ;

BERKS, M ;

MICKLEM, G ;

DURBIN, R ;

BATES, G ;

BRENNER, S ;

BECK, S ;

LEHRACH, H .

NATURE GENETICS, 1995, 10 (01) :67-76

[8] AGING, ENERGY, AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES [J].

BEAL, MF .

ANNALS OF NEUROLOGY, 1995, 38 (03) :357-366

[9] Huntington and DRPLA proteins selectively interact with the enzyme GAPDH [J].

Burke, JR ;

Enghild, JJ ;

Martin, ME ;

Jou, YS ;

Myers, RM ;

Roses, AD ;

Vance, JM ;

Strittmatter, WJ .

NATURE MEDICINE, 1996, 2 (03) :347-350

[10] SCA1 TRANSGENIC MICE - A MODEL FOR NEURODEGENERATION CAUSED BY AN EXPANDED CAG TRINUCLEOTIDE REPEAT [J].

BURRIGHT, EN ;

CLARK, HB ;

SERVADIO, A ;

MATILLA, T ;

FEDDERSEN, RM ;

YUNIS, WS ;

DUVICK, LA ;

ZOGHBI, HY ;

ORR, HT .

CELL, 1995, 82 (06) :937-948

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