Researchers identify the possible role of polyphosphate in dialysis-related amyloidosis

The long-term dialysis treatment is difficult for the body in many ways, but one of the most serious complications is dialysis-related amyloidosis, a disease characterized by an abnormal build-up of skin. aggregates of proteins – called amyloid fibrils – in joints, tissues and organs.

Although there is no cure, recent research by researchers at Osaka University has provided insight into the shape and aggregation of amyloid fibrils, allowing new therapeutic pathways to be identified. and preventative measures to further improve the lives of those affected.

In a study published in Proceedings of the National Academy of Sciences of the United States of AmericaResearchers at Osaka University have discovered that polyphosphate (polyP), which is a natural polymer in the body and a food and beverage additive, induces the formation of amyloid fibrils from β2 microglobulin proteins.

PolyPs play an important role in life as phosphorus storage. When renal function is normal, serum blood levels of β2 microglobulin remain low. However, β2 microglobulin is not effectively removed from the body at advanced stages of kidney disease. The implementation of dialysis further accentuates this problem because β2 microglobulin can not pbad through the dialysis membrane to be filtered.

Since the blood concentration of β2 microglobulin is higher when dialysis is used, the increased level of β2 microglobulin is the most important risk factor. However, the detailed mechanism triggering amyloid formation remains unclear. We wanted to study the effects of polyPs, compounds recently reported to be effective for other amyloid proteins, on the formation of amyloid fibrils from β2 microglobulin to determine how we can prevent it. "

Dr. Yuji Goto

To do this, the researchers monitored the effect of polyP on the formation of amyloid fibrils from β2 microglobulin under acidic and neutral conditions. Under acidic conditions, low polyP concentrations resulted in aggregates of proteins with an amyloid-fibril structure, but high concentrations of PolyP induced unstructured (or amorphous) aggregates.

"The results observed under acidic conditions were characteristic of a competitive mechanism," says Chun-ming Zhang, a former graduate student of the Protein Research Institute of Osaka University. . "On this basis, we hypothesized that the tendency to form amyloid fibrils or amorphous aggregates depends on the chemical environment."

However, under normal pH conditions, the results were quite different. The formed amyloid fibrils were thicker; polyP favored the formation of amyloid fibrils by aggregation of proteins by salting out effects.

This is the first evidence to determine how polyPs affect amyloid formation at different pHs. These findings have potential for clinical application as monitoring of polyP levels in people receiving long-term hemodialysis may provide information on the risk of developing dialysis-related amyloidosis in an individual.