Phosphorylation Signaling in APP Processing in Alzheimer's Disease

被引：74

作者：

Zhang, Tao ^{[1
]}

Chen, Dongmei ^{[1
]}

Lee, Tae Ho ^{[1
]}

机构：

[1] Fujian Med Univ, Sch Basic Med Sci, Inst Translat Med, Fujian Key Lab Translat Res Canc & Neurodegenerat, Fuzhou 350122, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; APP processing; phosphorylation; amyloid-beta; kinase; AMYLOID PRECURSOR PROTEIN; ALPHA-CONVERTING-ENZYME; PROLYL ISOMERASE PIN1; GAMMA-SECRETASE; CYTOPLASMIC DOMAIN; ECTODOMAIN PHOSPHORYLATION; TYROSINE PHOSPHORYLATION; NUCLEAR TRANSLOCATION; INTRACELLULAR DOMAIN; TERMINAL FRAGMENTS;

D O I：

10.3390/ijms21010209

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 abnormal accumulation of amyloid-beta (A beta) in the central nervous system is a hallmark of Alzheimer's disease (AD). The regulation of the processing of the single- transmembrane amyloid precursor protein (APP) plays an important role in the generation of A beta in the brain. The phosphorylation of APP and key enzymes involved in the proteolytic processing of APP has been demonstrated to be critical for modulating the generation of A beta by either altering the subcellular localization of APP or changing the enzymatic activities of the secretases responsible for APP processing. In addition, the phosphorylation may also have an impact on the physiological function of these proteins. In this review, we summarize the kinases and signaling pathways that may participate in regulating the phosphorylation of APP and secretases and how this further affects the function and processing of APP and A beta pathology. We also discuss the potential of approaches that modulate these phosphorylation-signaling pathways or kinases as interventions for AD pathology.

引用

页数：22

共 153 条

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