title: β-amyloid42 induces desensitization of CXC chemokine receptor-4 via formyl peptide receptor in neural stem/progenitor cells.
abstract: 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. Aβ(42) promoted the proliferation of NSPCs. Moreover, Aβ(42) (10-1000 nM) promoted the migration of NSPCs in a dose-dependent manner. The attraction of NSPCs toward Aβ(42) was significantly offset by 10 μM cyclosporin H, a potent and selective formyl peptide receptor antagonist. After incubation with Aβ(42) 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 Aβ(42) 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.
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Ze-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Keng-Hoe
authors.initials: KH
authors.lastname: Lok
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C486264:Cxcr4 protein, rat; D010446:Peptide Fragments; D019718:Receptors, CXCR4; D044042:Receptors, Formyl Peptide; C075222:amyloid beta-protein (1-42); C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2