Studies on the cross ‐interaction between hIAPP and Aβ25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

AbstractA wealth of epidemiological evidence indicates a strong link between type 2 diabetes (T2D) and Alzheimer's disease (AD). The fiber deposition with cross ‐β‐sheet structure formed by self‐aggregation and misfolding of amyloidogenic peptides is a common hallmark of both diseases. For the patients with T2D, the fibrils are mainly found in the islets of Langerhans that results from the accumulation of human islet amyloid polypeptide (hIAPP). The major component of aggregates located in the brain of AD patients is amyloid‐β (Aβ). Many biophysical and physiological properties are shared by hIAPP and Aβ, and both peptides show similar cytotoxic mechanisms. Therefore, it is meaningful to investigate the possible cross‐interactions of hIA PP and Aβ in both diseases. In this article, the segment 25–35 of Aβ was selected because Aβ25 –35 was a core region in the process of amyloid formation and showed similar aggregation tendency and toxicity with full ‐length Aβ. The electrospray ionization‐ion mobility‐mass spectrometry analysis and thioflavin T fluorescence kinetic analysis combined with transmission electron microscopy were used to explore the effects of the coexistence of Aβ25 –35 and hIAPP on the self ‐aggregation of both peptides and whether there was co‐assembly in fibrillation. The results indicated that the aggregation of hIAPP and Aβ25 –35 had two nucleation stages in the binary mixtures. hIAPP and A β25 –35 had a high binding ...
Source: Journal of Mass Spectrometry - Category: Chemistry Authors: Tags: RESEARCH ARTICLE Source Type: research