Protein aggregation diseases: pathogenicity and therapeutic perspectives

被引：598

作者：

Aguzzi, Adriano ^{[1
]}

O'Connor, Tracy ^{[1
]}

机构：

[1] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland

来源：

NATURE REVIEWS DRUG DISCOVERY | 2010年 / 9卷 / 03期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE INHIBITOR; FAMILIAL ALZHEIMERS-DISEASE; INTRANEURONAL A-BETA-42 ACCUMULATION; GATED SODIUM-CHANNELS; A-BETA BURDEN; PRION PROTEIN; MOUSE MODEL; TRANSGENIC MICE; MEMORY DEFICITS;

D O I：

10.1038/nrd3050

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A growing number of diseases seem to be associated with inappropriate deposition of protein aggregates. Some of these diseases - such as Alzheimer's disease and systemic amyloidoses - have been recognized for a long time. However, it is now clear that ordered aggregation of pathogenic proteins does not only occur in the extracellular space, but in the cytoplasm and nucleus as well, indicating that many other diseases may also qualify as amyloidoses. The common structural and pathogenic features of these diverse protein aggregation diseases is only now being fully understood, and may provide novel opportunities for overarching therapeutic approaches such as depleting the monomeric precursor protein, inhibiting aggregation, enhancing aggregate clearance or blocking common aggregation-induced cellular toxicity pathways.

引用

页码：237 / 248

页数：12

共 168 条

[51] Bace1 modulates myelination in the central and peripheral nervous system [J].

Hu, Xiangyou ;

Hicks, Caitlin W. ;

He, Wanxia ;

Wong, Philip ;

Macklin, Wendy B. ;

Trapp, Bruce D. ;

Yan, Riqiang .

NATURE NEUROSCIENCE, 2006, 9 (12) :1520-1525

[52] Islet amyloid: A critical entity in the pathogenesis of type 2 diabetes [J].

Hull, RL ;

Westermark, GT ;

Westermark, P ;

Kahn, SE .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (08) :3629-3643

[53] Identification of a novel aspartic protease (Asp 2) as β-secretase [J].

Hussain, I ;

Powell, D ;

Howlett, DR ;

Tew, DG ;

Week, TD ;

Chapman, C ;

Gloger, IS ;

Murphy, KE ;

Southan, CD ;

Ryan, DM ;

Smith, TS ;

Simmons, DL ;

Walsh, FS ;

Dingwall, C ;

Christie, G .

MOLECULAR AND CELLULAR NEUROSCIENCE, 1999, 14 (06) :419-427

[54] 1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel γ-secretase modulator, reduces brain β-amyloid pathology in a Transgenic mouse model of Alzheimer's disease without causing peripheral toxicity [J].

Imbimbo, Bruno P. ;

Del Giudice, Elda ;

Colavito, Davide ;

D'Arrigo, Antonello ;

Carbonare, Maurizio Dalle ;

Villetti, Gino ;

Facchinetti, Fabrizio ;

Volta, Roberta ;

Pietrini, Vladimiro ;

Baroc, Maria F. ;

Serneels, Lutgarde ;

De Strooper, Bart ;

Leon, Alberta .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 323 (03) :822-830

[55]

Imbimbo BP, 2009, CURR OPIN INVEST DR, V10, P721

[56] Persistent amyloidosis following suppression of Aβ production in a transgenic model of Alzheimer disease [J].

Jankowsky, JL ;

Slunt, HH ;

Gonzales, V ;

Savonenko, AV ;

Wen, JC ;

Jenkins, NA ;

Copeland, NG ;

Younkin, LH ;

Lester, HA ;

Younkin, SG ;

Borchelt, DR .

PLOS MEDICINE, 2005, 2 (12) :1318-1333

[57] Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease [J].

Janus, C ;

Pearson, J ;

McLaurin, J ;

Mathews, PM ;

Jiang, Y ;

Schmidt, SD ;

Chishti, MA ;

Horne, P ;

Heslin, D ;

French, J ;

Mount, HTJ ;

Nixon, RA ;

Mercken, M ;

Bergeron, C ;

Fraser, PE ;

St George-Hyslop, P ;

Westaway, D .

NATURE, 2000, 408 (6815) :979-982

[58] Conformation-dependent anti-amyloid oligomer antibodies [J].

Kayed, Rakez ;

Glabe, Charles G. .

AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT C, 2006, 413 :326-344

[59] BACE1 regulates voltage-gated sodium channels and neuronal activity [J].

Kim, Doo Yeon ;

Carey, Bryce W. ;

Wang, Haibin ;

Ingano, Laura A. M. ;

Binshtok, Alexander M. ;

Wertz, Mary H. ;

Pettingell, Warren H. ;

He, Ping ;

Lee, Virginia M. -Y. ;

Woolf, Clifford J. ;

Kovacs, Dora M. .

NATURE CELL BIOLOGY, 2007, 9 (07) :755-U43

[60] Immunization with Amyloid-β Attenuates Inclusion Body Myositis-Like Myopathology and Motor Impairment in a Transgenic Mouse Model [J].

Kitazawa, Masashi ;

Vasilevko, Vitaly ;

Cribbs, David H. ;

LaFerla, Frank M. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (19) :6132-6141

← 1 2 3 4 5 6 7 8 9 10 →