Rationalizing the Role of Monosodium Glutamate in the Protein Aggregation Through Biophysical Approaches: Potential Impact on Neurodegeneration

Monosodium glutamate (MSG) is the world’s most extensively used food additive and is generally recognized as safe according to FDA. However, it is well reported that MSG is associated with number of neurological diseases and in turn neurological diseases are associated with protein aggregation. This study rationalized the role of MSG in protein misfolding and aggregation using different biophysical techniques such, as absorption, far-UV CD, DLS, ITC. Kinetic measurements revealed that MSG causes significant enhancement of aggregation of BSA through nucleation-dependent polymerization mechanism. Also CTAB-BSA aggregation is enhanced by MSG significantly. MSG-induced BSA aggregation also exhibits the formation of irreversible aggregates, temperature dependence Non-Arrhenius behavior and enhancement of hydrodynamic diameter. From the isothermal titration calorimetry measurement, significant endothermic heat of interaction of BSA-MSG also favors the MSG is coupled with protein aggregation. Enthalpy change, entropy change and Gibbs free energy change calculated were largely positive. Furthermore, even low concentration of MSG is involved in the unfolding of secondary structure of protein with the disappearance of original peaks and formation of unique peak in the far-UV CD which is attention-grabbing observation. This is the first investigation which links the dietary MSG with protein misfolding and aggregation and thus will be very instrumental in understanding the mechanism of MSG-related various human physiological as well as neurological diseases.