β-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module
β-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module
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DOI：
10.1074/jbc.m011161200
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发表时间：
2001-06-01
影响因子：
4.8
通讯作者：
Ozenberger, BA
中科院分区：
文献类型：
--
作者：
Kajkowski, EM;Lo, CF;Ozenberger, BA
阿尔茨海默病中神经元的变性是由β-淀粉样肽通过多种机制介导的，其中包括由未鉴定的信号传导事件刺激的推定的凋亡组分。本报告描述了一种新的β-淀粉样肽结合蛋白（表示BBP）含有G蛋白偶联模块。BBP是含有这种保守结构的三种蛋白质家族的成员之一。BBP亚型在体外以高亲和力和特异性结合人β-淀粉样肽。BBP在细胞培养物中的表达诱导半胱天冬酶依赖性对β-淀粉样肽毒性的脆弱性。信号传导缺陷显性负性BBP突变体的表达抑制了人Ntera-2神经元对β-淀粉样肽介导的毒性的敏感性。这些发现表明BBP是神经毒性β-淀粉样肽的靶点，并为阿尔茨海默病的分子病理生理学提供了新的见解。
Degeneration of neurons in Alzheimer's disease is mediated by beta -amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta -amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta -amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta -amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta -amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta -amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.