Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease.
Alzheimer disease (AD) is the most common neurodegenerative disease, affecting approx 4 million people in the United States in the year 2000 alone. Amyloid beta (Abeta) deposition, activated glial cells, and neuritic degeneration are the characteristic features of AD. Although the precise cause of AD has yet to be determined, a bulk of evidence suggests that inflammatory responses elicited by elevated Abeta peptides play an important role in the pathogenic process of the disease. In AD brain, mononuclear phagocytes (microglia) accumulate at the sites of Abeta peptide deposition. In vitro, Abeta peptides activate mononuclear phagocytes to release neurotoxic mediators. A number of cell-surface molecules have been reported to act as putative receptors for Abeta peptides, among which the G protein-coupled formyl peptide receptor-like 1 (FPRL1) and its mouse homolog FPR2 have been shown to be expressed by activated microglial cells and mediate the chemotactic activity of the 42 amino acid form of Abeta (Abeta42). FPRL1 also participates in Abeta42 internalization in macrophages and its cytotoxicity for neuronal cells. Therefore, FPRL1 may be involved in the inflammatory aspects of AD. This review discusses recent findings relevant to the function and regulation of FPRL1/FPR2 in mononuclear phagocytes by pro- and antiinflammatory signals and its potential as a therapeutic target in AD.
Iribarren
Pablo
P
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560, Frederick, MD 21702, USA.
Zhou
Ye
Y
Hu
Jinyue
J
Le
Yingying
Y
Wang
Ji Ming
JM
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D010586:Phagocytes / Q000378:metabolism* / Q000473:pathology; D044042:Receptors, Formyl Peptide / Q000276:immunology* / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; C105101:FPR2 protein, human; C469985:FPR3 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C481578:formyl peptide receptor 2, mouse