Screening potential inhibitors against Alzheimer's amyloidosis using electrospray ionization mass spectrometry

Abstract

Alzheimer's disease (AD) is associated with neurodegeneration, premature death and has a major impact on health along with economical ramifications in Western world. The prevailing hypotheses regarding the cause of AD have centered on the amyloid beta protein (Aβ)-containing senile plaques. In light of the suggested link between oxidative stress and Aβ's aggregation, the use of antioxidants as a therapeutic regime for protection against the risk of this disease has to be explored. The binding of Aβ with endogenous or plant-derived bioactive antioxidants via the formation of noncovalent complexes has been studied by electrospray ionization (ESI) mass spectrometry (MS). The stability and specificity of the complexes has been examined under several experimental parameters, while the topology of the interacting species has been revealed by proteolytic mapping, in conjunction with ESI Fourier Transform Ion Cyclotron (FTICR) MS analysis. The ligands that bind to Aβ could be used as potential aggregation inhibitors and serve as lead compounds for the synthesis of anti-amyloidogenic agents against AD.