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标题：β-Amyloid42 Induces Desensitization of CXC Chemokine Receptor-4 via Formyl Peptide Receptor in Neural Stem/Progenitor Cells
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作者：Can Zhang ; Ze-Jian Wang ; Keng-Hoe Lok 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：2
页码：131-138
DOI：10.1248/bpb.35.131
出版社：The Pharmaceutical Society of Japan
摘要：The deposition of β-amyloid (Aβ) plaques and progressive loss of neurons are two main characteristics of Alzheimer’s disease (AD). Supplement of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the neurodegenerative diseases. However, hostile microenvironment of neurodegenerative brain is harmful for the neuroregeneration. Aβ₄₂ promoted the proliferation of NSPCs. Moreover, Aβ₄₂ (10—1000 n M ) promoted the migration of NSPCs in a dose-dependent manner. The attraction of NSPCs toward Aβ₄₂ was significantly offset by 10 μ M cyclosporin H, a potent and selective formyl peptide receptor antagonist. After incubation with Aβ₄₂ for 9 d, the migration ability of NSPCs was significantly decreased ( p <0.05). The expression of formyl peptide receptor (FPR) and CXC chemokine receptor-4 (CXCR4) were significantly decreased in NSPCs. The expression of G protein-coupled receptor kinase 2 (GRK2) was up-regulated on the membrane of NSPCs correspondingly. Our results suggested that Aβ₄₂ decreases the migratory capacity of NSPCs by FPR heterologous desensitization after long time incubation, and GRK2 in NSPCs may be responsible for the damaged migratory capacity.
关键词：β-amyloid42;neural stem cell;progenitor cell;formyl peptide receptor;G protein-coupled receptor kinase 2