Aim: 

Glycosaminoglycans (GAGs) are routinely found associated with amyloid deposits in most amyloid diseases, and there is evidence to support their active role in amyloid fibril formation. The purpose of this study was to obtain structural insight into GAGs-protein interactions and to determine whether the presence of GAGs affects the amyloid aggregation process and cytotoxicity.

Methods: 

we analyze the effect of heparin and certain other GAGs on the kinetics of fibril formation and aggregate cytotoxicity of the amyloid forming W7FW14 apomyoglobin mutant.

Results: 

The results were compared with those obtained in the presence of differently charged polymers, i.e., polylysine, polyarginine, dextran and dextran sulphate. Heparin and dextran sulphate strongly stimulated aggregation into amyloid fibrils, abolishing the lag-phase normally detected following the kinetics of the process. Moreover, the protein aggregates were found harmless. Dextran, polyarginine and polylysine did not affect the aggregation rate and the early aggregates were found highly cytotoxic. Thus, the presence of negative charged groups seems to be essential for the stimulatory effect on amyloid fibril formation and to induce the protein to rapidly reach the harmless conformation. However, heparin induces amyloid fibril formation also in wild type apomyoglobin, a protein that normally does not show any tendency to aggregate.

Conclusion: 

These data show that glycosaminoglicans could play a different role of in amyloidosis, as pathological chaperones and safe compounds. Therefore, it is not clear their effectiveness as therapeutic agents to prevent or slow the progression of amyloidogenic disorders and carefulness is required in their use.