Amyloid β42 activates a G-protein-coupled chemoattractant receptor, FPR-Like-1
Amyloid β42 activates a G-protein-coupled chemoattractant receptor, FPR-Like-1
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DOI：
10.1523/jneurosci.21-02-j0003.2001
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发表时间：
2001-01-15
影响因子：
5.3
通讯作者：
Wang, JM
中科院分区：
文献类型：
--
作者：
Le, YY;Gong, WH;Wang, JM
淀粉样蛋白β（A β）是阿尔茨海默病（AD）发病机制的主要贡献者。虽然A β已被报道为直接神经毒性，但它也通过激活在老年斑内和周围积聚的单核吞噬细胞（小胶质细胞）引起间接神经元损伤。在这项研究中，我们表明，42个氨基酸形式的β淀粉样肽，A α（42），是一种趋化性激动剂的七个跨膜，G蛋白偶联受体命名为FPR样1（FPRL 1），这是表达在人类单核吞噬细胞。此外，FPRL 1在AD患者脑组织中浸润老年斑的炎性细胞中以高水平表达。因此，FPRL 1可能介导AD中观察到的炎症，并且是开发治疗药物的潜在靶点。
Amyloid beta (A beta) is a major contributor to the pathogenesis of Alzheimer's disease (AD). Although A beta has been reported to be directly neurotoxic, it also causes indirect neuronal damage by activating mononuclear phagocytes (microglia) that accumulate in and around senile plaques. In this study, we show that the 42 amino acid form of beta amyloid peptide, A alpha (42), is a chemotactic agonist for a seven-transmembrane, G-protein-coupled receptor named FPR-Like-1 (FPRL1), which is expressed on human mononuclear phagocytes. Moreover, FPRL1 is expressed at high levels by inflammatory cells infiltrating senile plaques in brain tissues from AD patients. Thus, FPRL1 may mediate inflammation seen in AD and is a potential target for developing therapeutic agents.