Counteraction of the cetyltrimethylammonium bromide-induced protein aggregation by heparin: Potential impact on protein aggregation and neurodegenerative diseases using biophysical approaches

Heparin, a member of the glycosaminoglycan (GAG) family, is an extremely acidic sulfur-containing polysaccharide which has been suggested to be coupled with protein aggregation-related diseases includ-ing Alzheimer's, Parkinson's and Prion diseases. Here, we study the effect of heparin on the cetyltrimethy-lammonium bromide (CTAB)-induced aggregation of bovine serum albumin (BSA) exploiting biophysical approaches. Kinetic measurements indicated that heparin caused complete inhibition of CTAB-induced aggregation of protein with a significant decrease in the apparent rate constant. Far-and near-UV CD measurements depicted that CTAB behaves as a protein-aggregating agent. However, the perturbation of secondary and tertiary structure-induced by CTAB and the CTAB-induced amyloid formation of pro-tein were prevented by heparin. ITC measurements revealed that enhancement of aggregation induced by CTAB was as a result of sequential binding in which CTAB binds with the protein and accompanied by exothermic heat of interaction. ITC measurements also showed that CTAB and heparin form com-plex while the complex does not bind with protein. Thus, we hypothesize that CTAB-Heparin complex is engaged in the inhibition of protein aggregation. Therefore, the mechanism of action of CTAB-heparin complex in inhibition of protein aggregation may be used as a basis of the development of therapeutic strategies of various neurodegenerative complications.(c) 2022 Elsevier B.V. All rights reserved.