Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis

Accumulation of fibrils composed of amyloid A in tissues resulting in displ acement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand imm unoglobulin superfamily cell surface molecule, is a receptor for the amyloi dogenic form of serum amyloid A. Interactions between RAGE and amyloid A in duced cellular perturbation. In a mouse model, amyloid A accumulation, evid ence of cell stress and expression of RAGE were closely linked. Antagonizin g RAGE suppressed cell stress and amyloid deposition in mouse spleens. Thes e data indicate that RAGE is a potential target for inhibiting accumulation of amyloid A and for limiting cellular dysfunction induced by amyloid A.