Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1.
Amyloid beta (Abeta) is a major contributor to the pathogenesis of Alzheimer's disease (AD). Although Abeta 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, Abeta(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.
Le
Y
Y
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, International Corporation Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Gong
W
W
Tiffany
H L
HL
Tumanov
A
A
Nedospasov
S
S
Shen
W
W
Dunlop
N M
NM
Gao
J L
JL
Murphy
P M
PM
Oppenheim
J J
JJ
Wang
J M
JM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D015693:Gene Products, nef / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016229:Amyloid beta-Peptides; C105101:FPR2 protein, human; D015693:Gene Products, nef; D010446:Peptide Fragments; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C075222:amyloid beta-protein (1-42); D009240:N-Formylmethionine Leucyl-Phenylalanine; D019204:GTP-Binding Proteins; D002118:Calcium