Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain

被引：2254

作者：

DiFiglia, M

Sapp, E

Chase, KO

Davies, SW

Bates, GP

Vonsattel, JP

Aronin, N

机构：

[1] UNIV LONDON UNIV COLL, DEPT ANAT & DEV BIOL, LONDON WC1E 6BT, ENGLAND

[2] UNITED MED & DENT SCH GUYS & ST THOMAS HOSP, GUYS HOSP, LONDON SE1 7EH, ENGLAND

[3] UNIV MASSACHUSETTS, MED CTR, DEPT MED & CELL BIOL, WORCESTER, MA 01655 USA

来源：

SCIENCE | 1997年 / 277卷 / 5334期

关键词：

D O I：

10.1126/science.277.5334.1990

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The cause of neurodegeneration in Huntington's disease (HD) is unknown. Patients with HD have an expanded NH2-terminal polyglutamine region in huntingtin. An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions (NIIs) and dystrophic neurites (DNs) in the HD cortex and striatum, which are affected in HD, and polyglutamine length influenced the extent of huntingtin accumulation in these structures. Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD.

引用

页码：1990 / 1993

页数：4

共 37 条

[11] Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation [J].

Davies, SW ;

Turmaine, M ;

Cozens, BA ;

DiFiglia, M ;

Sharp, AH ;

Ross, CA ;

Scherzinger, E ;

Wanker, EE ;

Mangiarini, L ;

Bates, GP .

CELL, 1997, 90 (03) :537-548

[12] MORPHOMETRIC DEMONSTRATION OF ATROPHIC CHANGES IN THE CEREBRAL-CORTEX, WHITE MATTER, AND NEOSTRIATUM IN HUNTINGTONS-DISEASE [J].

DELAMONTE, SM ;

VONSATTEL, JP ;

RICHARDSON, EP .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1988, 47 (05) :516-525

[13] HUNTINGTIN IS A CYTOPLASMIC PROTEIN ASSOCIATED WITH VESICLES IN HUMAN AND RAT-BRAIN NEURONS [J].

DIFIGLIA, M ;

SAPP, E ;

CHASE, K ;

SCHWARZ, C ;

MELONI, A ;

YOUNG, C ;

MARTIN, E ;

VONSATTEL, JP ;

CARRAWAY, R ;

REEVES, SA ;

BOYCE, FM ;

ARONIN, N .

NEURON, 1995, 14 (05) :1075-1081

[14] TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE [J].

DUYAO, M ;

AMBROSE, C ;

MYERS, R ;

NOVELLETTO, A ;

PERSICHETTI, F ;

FRONTALI, M ;

FOLSTEIN, S ;

ROSS, C ;

FRANZ, M ;

ABBOTT, M ;

GRAY, J ;

CONNEALLY, P ;

YOUNG, A ;

PENNEY, J ;

HOLLINGSWORTH, Z ;

SHOULSON, I ;

LAZZARINI, A ;

FALEK, A ;

KOROSHETZ, W ;

SAX, D ;

BIRD, E ;

VONSATTEL, J ;

BONILLA, E ;

ALVIR, J ;

CONDE, JB ;

CHA, JH ;

DURE, L ;

GOMEZ, F ;

RAMOS, M ;

SANCHEZRAMOS, J ;

SNODGRASS, S ;

DEYOUNG, M ;

WEXLER, N ;

MOSCOWITZ, C ;

PENCHASZADEH, G ;

MACFARLANE, H ;

ANDERSON, M ;

JENKINS, B ;

SRINIDHI, J ;

BARNES, G ;

GUSELLA, J ;

MACDONALD, M .

NATURE GENETICS, 1993, 4 (04) :387-392

[15]

FOLSTEIN SE, 1989, HUNTINGTONS DIS DISO, P1

[16]

FUNATA N, 1990, CLIN NEUROPATHOL, V9, P89

[17] Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract [J].

Goldberg, YP ;

Nicholson, DW ;

Rasper, DM ;

Kalchman, MA ;

Koide, HB ;

Graham, RK ;

Bromm, M ;

KazemiEsfarjani, P ;

Thornberry, NA ;

Vaillancourt, JP ;

Hayden, MR .

NATURE GENETICS, 1996, 13 (04) :442-449

[18] EVIDENCE FOR DEGENERATIVE AND REGENERATIVE CHANGES IN NEOSTRIATAL SPINY NEURONS IN HUNTINGTONS-DISEASE [J].

GRAVELAND, GA ;

WILLIAMS, RS ;

DIFIGLIA, M .

SCIENCE, 1985, 227 (4688) :770-773

[19] NEURONAL INTRANUCLEAR INCLUSION DISEASE IN IDENTICAL-TWINS [J].

HALTIA, M ;

SOMER, H ;

PALO, J ;

JOHNSON, WG .

ANNALS OF NEUROLOGY, 1984, 15 (04) :316-321

[20] NEURONAL LOSS IN LAYERS-V AND LAYERS-VI OF CEREBRAL-CORTEX IN HUNTINGTONS-DISEASE [J].

HEDREEN, JC ;

PEYSER, CE ;

FOLSTEIN, SE ;

ROSS, CA .

NEUROSCIENCE LETTERS, 1991, 133 (02) :257-261

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