Elevated amyloidoses of human IAPP and amyloid beta by lipopolysaccharide and their mitigation by carbon quantum dots

Kairi Koppel, Huayuan Tang, Ibrahim Javed, Mohammad Reza Parsa, Monika Mortimer, Thomas P. Davis, Sijie Lin, Alan Chaffee, Feng Ding, Pu Chun Ke

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Type 2 diabetes (T2D) and Alzheimer's disease (AD) represent two most prevalent amyloid diseases with a significant global burden. Pathologically, T2D and AD are characterized by the presence of amyloid plaques consisting primarily of toxic human islet amyloid polypeptide (IAPP) and amyloid beta (Aβ). It has been recently revealed that the gut microbiome plays key functions in the pathological progression of neurological disorders through the production of bacterial endotoxins, such as lipopolysaccharide (LPS). In this study, we examined the catalytic effects of LPS on IAPP and Aβ amyloidoses, and further demonstrated their mitigation with zero-dimensional carbon quantum dots (CQDs). Whereas LPS displayed preferred binding with the N-terminus of IAPP and the central hydrophobic core and C-terminus of Aβ, CQDs exhibited propensities for the amyloidogenic and C-terminus regions of IAPP and the N-terminus of Aβ, accordingly. The inhibitory effect of CQDs was verified by an embryonic zebrafish model exposed to the peptides and LPS, where impaired embryonic hatching was rescued and production of reactive oxygen species in the organism was suppressed by the nanomaterial. This study revealed a robust synergy between LPS and amyloid peptides in toxicity induction, and implicated CQDs as a potential therapeutic against the pathologies of T2D and AD.

Original languageEnglish
Pages (from-to)12317-12328
Number of pages12
JournalNanoscale
Volume12
Issue number23
DOIs
Publication statusPublished - 21 Jun 2020

Cite this