哺乳动物淀粉样物质解聚活性的发现与鉴定。
Discovery and characterization of a mammalian amyloid disaggregation activity.
机构信息
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
出版信息
Protein Sci. 2010 Apr;19(4):836-46. doi: 10.1002/pro.363.
Abstract
The formation of amyloid, a cross-beta-sheet fibrillar aggregate, is associated with a variety of aging-associated degenerative diseases. Herein, we report the existence of a mammalian amyloid disaggregase activity that is present in all tissues and cell types tested. Homogenates from mammalian tissues and cell lines are able to disaggregate amyloid fibrils composed of amyloid beta (A beta)(1-40) or the 8 kDa plasma gelsolin fragment. The mammalian disaggregase activity is sensitive to proteinase K digestion and can be uncoupled from proteolysis activity using a protease inhibitor cocktail. Amyloid disaggregation and proteolysis activities are remarkably resistant to changes in temperature and pH. Identification and manipulation of the proteins responsible for the amyloid disaggregation/degradation activities offers the possibility of ameliorating aggregation-associated diseases.
摘要
淀粉样蛋白的形成是一种交叉β-折叠纤维状聚集物，与各种与衰老相关的退行性疾病有关。在此，我们报告了哺乳动物淀粉样蛋白去聚集酶活性的存在，该活性存在于所有测试的组织和细胞类型中。来自哺乳动物组织和细胞系的匀浆能够使由淀粉样β（Aβ）（1-40）或 8 kDa 血浆凝胶蛋白片段组成的淀粉样纤维解聚。哺乳动物的去聚集酶活性对蛋白酶 K 的消化敏感，并可以使用蛋白酶抑制剂混合物将其与蛋白水解活性解偶联。淀粉样蛋白的解聚和蛋白水解活性对温度和 pH 值的变化具有很强的抵抗力。鉴定和操纵负责淀粉样蛋白解聚/降解活性的蛋白质为改善与聚集相关的疾病提供了可能。
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