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Potential role of the formyl peptide receptor‐like 1 (FPRL1) in inflammatory aspects of Alzheimer’s disease
Author(s) -
Cui Youhong,
Le Yingying,
Yazawa Hiroshi,
Gong Wanghua,
Wang Ji Ming
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.4.628
Subject(s) - formyl peptide receptor , proinflammatory cytokine , senile plaques , neurodegeneration , biology , microglia , receptor , pathogenesis , transmembrane protein , inflammation , microbiology and biotechnology , alzheimer's disease , amyloid (mycology) , immunology , disease , chemotaxis , biochemistry , medicine , botany
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by the presence of multiple senile plaques in the brain tissue, which are also associated with considerable inflammatory infiltrates. Although the precise mechanisms of the pathogenesis of AD remain to be determined, the overproduction and precipitation of a 42 amino acid form of β amyloid (Aβ 42 ) in plaques have implicated Aβ in neurodegeneration and proinflammatory responses seen in the AD brain. Our recent studies revealed that the activation of formyl peptide receptor‐like 1 (FPRL1), a seven‐transmembrane, G‐protein‐coupled receptor, by Aβ 42 may be responsible for accumulation and activation of mononuclear phagocytes (monocytes and microglia). We further found that upon binding FPRL1, Aβ 42 was rapidly internalized into the cytoplasmic compartment in the form of Aβ 42 /FPRL1 complexes. Persistent exposure of FPRL1‐expressing cells to Aβ 42 resulted in intracellular retention of Aβ 42 /FPRL1 complexes and the formation of Congo‐red‐positive fibrils in mononuclear phagocytes. Our observations suggest that FPRL1 may not only mediate the proinflammatory activity of Aβ 42 but also actively participate in Aβ 42 uptake and the resultant fibrillar formation. Therefore, FPRL1 may constitute an additional molecular target for the development of therapeutic agents for AD.