期刊
FEBS JOURNAL
卷 277, 期 7, 页码 1585-1596出版社
WILEY
DOI: 10.1111/j.1742-4658.2010.07566.x
关键词
alpha-secretase; amyloid precursor protein; Alzheimer's disease; domain structure; neuroprotection; shedding; synaptogenesis; TACE
资金
- National Genome Research Network (NGFN), Forderkennzeichen [FKZ01GS08130]
A decade ago, a disintegrin and metalloproteinase 10 (ADAM10) was identified as an alpha-secretase and as a key proteinase in the processing of the amyloid precursor protein. Accordingly, the important role that it plays in Alzheimer's disease was manifested. Animal models with an overexpression of ADAM10 revealed a beneficial profile of the metalloproteinase with respect to learning and memory, plaque load and synaptogenesis. Therefore, ADAM10 presents a worthwhile target with respect to the treatment of a neurodegenerative disease such as Morbus Alzheimer. Initially, ADAM10 was suggested to be an enzyme, shaping the extracellular matrix by cleavage of collagen type IV, or to be a tumour necrosis factor alpha convertase. In a relatively short time, a wide variety of additional substrates (with amyloid precursor protein probably being the most prominent) has been identified and the search is still ongoing. Hence, any side effects concerning the therapeutic enhancement of ADAM10 alpha-secretase activity have to be considered. The present review summarizes our knowledge about the structure and function of ADAM10 and highlights the opportunities for enhancing the expression and/or activity of the alpha-secretase as a therapeutic target.
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