Protein aggregation diseases: pathogenicity and therapeutic perspectives

被引:587
作者
Aguzzi, Adriano [1 ]
O'Connor, Tracy [1 ]
机构
[1] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland
基金
欧洲研究理事会; 瑞士国家科学基金会;
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
收藏
页码:237 / 248
页数:12
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