Glycosaminoglycans inhibit neurodegenerative effects of serum amyloid P component in vitro

Serum amyloid P component, a member of pentraxin serum protein family, has been suggested to contribute to the progression of neurodegeneration including Alzheimer's disease by binding to β-amyloid fibrils leading to an increased stability of the deposits against proteolytic degradation and by inducing neuronal apoptosis. Here, we show that glycosaminoglycans inhibit both the serum amyloid P component-β-amyloid interaction and the neurotoxic effect of serum amyloid P component. These effects correlate with the structure of glycosaminoglycans and show different structure-activity relationship in the case of the two different effects. While the efficacy of the inhibition on the serum amyloid P component-induced cell death increases with the uronic acid content, the inhibitory activity on the serum amyloid P component-β-amyloid interaction decreases with the increasing uronic acid content of the glycosaminoglycans. The inhibitory effect of glycosaminoglycans on the interaction between the first component of the complement cascade (C1q) and β-amyloid shows a similar structure-activity relationship as on the serum amyloid P component-β-amyloid interaction. This suggests that glycosaminoglycans interfere with the binding site on β-amyloid for serum amyloid P component and C1q. The functional consequence of this binding has been demonstrated by heparin which promotes the proteolysis of β-amyloid in vitro in the presence of serum amyloid P component. Our results suggest that glycosaminoglycans might have therapeutical potential on the neurodegeneration reducing its progress.