期刊
PATHOBIOLOGY OF AGING AND AGE-RELATED DISEASES
卷 5, 期 1, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.3402/pba.v5.25796
关键词
APP; AbPP proteolysis; endosome; LINGO; trafficking; Alzheimer's disease
类别
资金
- National Institute of Aging [1R01 AG21127, R21 AG02647]
- Alzheimer's Disease Association [IIRG-00-1935]
- Alzheimer's Disease Research Center [AG05136]
- Adult Changes in Thought Study [AG006781]
- Morris K Udall Center of Excellence for Parkinson's Disease Research [NS062684]
Sequential proteolytic cleavages of amyloid-b protein precursor (AbPP) by b-secretase and g-secretase generate amyloid b (Ab) peptides, which are thought to contribute to Alzheimer's disease (AD). Much of this processing occurs in endosomes following endocytosis of AbPP from the plasma membrane. However, this pathogenic mode of processing AbPP may occur in competition with lysosomal degradation of AbPP, a common fate of membrane proteins trafficking through the endosomal system. Following up on published reports that LINGO-1 binds and promotes the amyloidogenic processing of AbPP we have examined the consequences of LINGO-1/AbPP interactions. We report that LINGO-1 and its paralogs, LINGO-2 and LINGO-3, decrease processing of AbPP in the amyloidogenic pathway by promoting lysosomal degradation of AbPP. We also report that LINGO-1 levels are reduced in AD brain, representing a possible pathogenic mechanism stimulating the generation of Ab peptides in AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据