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(Journal of Leukocyte Biology. 2002;72:628-635.)
© 2002 by Society for Leukocyte Biology

Potential role of the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer’s disease

Youhong Cui^*,, Yingying Le, Hiroshi Yazawa, Wanghua Gong and Ji Ming Wang

^* Biochemistry Section, Lanzhou Military Medical University, Lanzhou, People’s Republic of China; and
Laboratory of Molecular Immunoregulation and
Intramural Research Support Program, SAIC Frederick, Center for Cancer Research, National Cancer Institute at Frederick, Maryland

Correspondence: Dr. Ji Ming Wang, LMI, CCR, NCI-Frederick, Building 560, Room 31-40, Frederick, MD 21702. E-mail: wangji{at}mail.ncifcrf.gov

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 ß amyloid (Aß₄₂) in plaques have implicated Aß 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 Aß₄₂ may be responsible for accumulation and activation of mononuclear phagocytes (monocytes and microglia). We further found that upon binding FPRL1, Aß₄₂ was rapidly internalized into the cytoplasmic compartment in the form of Aß₄₂/FPRL1 complexes. Persistent exposure of FPRL1-expressing cells to Aß₄₂ resulted in intracellular retention of Aß₄₂/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 Aß₄₂ but also actively participate in Aß₄₂ uptake and the resultant fibrillar formation. Therefore, FPRL1 may constitute an additional molecular target for the development of therapeutic agents for AD.

Key Words: NSAID • central nervous system • Aß • macrophage • microglia

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