A multi-talented secreted protein.
A multi-talented secreted protein.
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一种多才多艺的分泌蛋白。
DOI：
10.1016/s0166-2236(00)01936-6
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发表时间：
2001
影响因子：
15.9
通讯作者：
Mattson,MP
中科院分区：
文献类型：
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作者：
Mattson,MP
什么样的分泌蛋白在学习和记忆中起作用，促进神经元存活和轴突生长，刺激细胞增殖，调节小胶质细胞反应，并能调节血液凝固和脂蛋白代谢？作为一个提示，它是来自一个轴突运输的整合膜蛋白，在阿尔茨海默病的发病机制中起着核心作用。这种多功能蛋白质是β-淀粉样前体蛋白（sAPP）的分泌形式。对这种分泌蛋白的研究历史是，它们最初在一种组织中被发现，随后被证明具有广泛的影响范围。例如，成纤维细胞生长因子和骨形态发生蛋白作用于脑细胞，脑源性神经营养因子调节免疫细胞，睫状神经营养因子调节肝脏生理学。APP是一种大的（695-770个氨基酸）单通道膜蛋白，最初在脑中研究，因为它是40-42个氨基酸的淀粉样β肽的来源，淀粉样β肽是阿尔茨海默病患者脑中斑块的主要致病成分。然而，APP在细胞表面的酶促裂解释放大量分泌形式的APP（sAPP）。虽然sAPP的许多不同的生物学效应已被记录，但尚未鉴定出抑制细胞对其反应的受体。现在，Eschago-Garci et al. 1提供了强有力的证据，证明sAPP选择性结合A类清道夫受体（SR-A），从而与低密度脂蛋白（LDL）竞争细胞摄取。由于SR-A介导的巨噬细胞对LDL的摄取被认为是血管中动脉粥样硬化斑块形成的重要事件，因此sAPP可能在抑制动脉粥样硬化过程中发挥作用。除了结合SR-A之外，含有Kunitz蛋白酶抑制剂结构域的sAPP形式也可以结合LDL相关受体（LRP）。因此，sAPP正在成为脂蛋白代谢的重要参与者，
What secreted protein plays a role in learning and memory, promotes neuronal survival and neurite outgrowth, stimulates cell proliferation, modulates microglial reactivity, and can regulate blood coagulation and lipoprotein metabolism? As a hint, it is derived from an axonally transported integral membrane protein that plays a central role in the pathogenesis of Alzheimer’s disease. This multi-talented protein is the secreted form of β-amyloid precursor protein (sAPP). The history of research on such secreted proteins is that they are initially discovered in one tissue and are subsequently shown to have a broad sphere of influence. For example, fibroblast growth factor and bone morphogenetic protein act on brain cells, brain-derived neurotrophic factor modulates immune cells, and ciliary neurotrophic factor regulates liver physiology. APP is a large (695–770 amino acid) single-pass membrane protein that was initially studied in the brain because it is the source of the 40–42 amino acid amyloid β-peptide, the major pathogenic component of plaques in the brains of patients with Alzheimer’s disease. However, an enzymatic cleavage of APP at the cell surface releases a large secreted form of APP (sAPP). Although many different biological effects of sAPP have been documented, no receptors that transduce cellular responses to it have been identified. Santiago-Garci et al. 1 now provide strong evidence that sAPP selectively binds to the class A scavenger receptor (SR-A) and thereby competes with low-density lipoprotein (LDL) for cellular uptake. Because SR-A-mediated uptake of LDL by macrophages is thought to be an important event in the formation of atherosclerotic plaques in blood vessels, sAPP might play a role in suppressing the process of atherosclerosis. In addition to binding SR-A, forms of sAPP that contain a Kunitz protease inhibitor domain can also bind the LDL-related receptor (LRP). Thus, sAPP is emerging as an important player in lipoprotein metabolism, a process