Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer's disease

被引：154

作者：

Ling, Y ^{[1
]}

Morgan, K ^{[1
]}

Kalsheker, N ^{[1
]}

机构：

[1] Univ Nottingham, Queens Med Ctr, Inst Genet, Div Clin Chem, Nottingham NG7 2UH, England

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2003年 / 35卷 / 11期

关键词：

amyloid precursor protein; proteolytic processing; Alzheimer's disease;

D O I：

10.1016/S1357-2725(03)00133-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The processing of amyloid precursor protein (APP) generates amyloid-beta (Abeta) peptides 1-40 and 1-42. The latter is neurotoxic and its accumulation results in amyloid fibril formation and the generation of senile plaques, the hallmark of Alzheimer's disease (AD). Whilst there has been considerable progress made in understanding the generation of Abeta by alpha-, beta- and gamma-secretase activity on APP, recently enzymes involved in the degradation of Abeta have been identified including neprilysin and insulin-degrading enzyme (IDE). We review the pathways involved in proteolytic processing of APP and discuss the potential implications of aberrant proteolysis on neurodegeneration. It is conceivable that single nucleotide polymorphisms (SNPs) in the regulatory regions of genes in these proteolytic cascades, which alter their expression, could contribute to some of the age-related changes seen in AD. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1505 / 1535

页数：31

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