Decabromodiphenyl ethane induces locomotion neurotoxicity and potential Alzheimer’s disease risks through intensifying amyloid-beta deposition by inhibiting transthyretin/transthyretin-like proteins

Abstract

As a major alternative to traditional brominated flame retardants (BFRs), decabromodiphenyl ethane (DBDPE) is widely used and has been commonly detected in various environmental media and organisms. Few previous studies have focused on DBDPE-induced locomotion neurotoxicity, and the exact molecular mechanisms and related health risks remain unclear. In this study, we first analyzed the locomotion indicators of nematodes following DBDPE exposure, demonstrated that DBDPE caused locomotion neurotoxicity, and identified that a series of the transthyretin (TTR)-like genes participated in the regulation of nematode motility by transcriptomic analysis, gene transcription validation and TTR-like mutant verification. Subsequently, this study demonstrated that DBDPE exacerbated amyloid-beta (Aβ) deposition by repressing TTR/TTR-like gene transcription based on Alzheimer’s disease (AD) model nematodes and human SH-SY5Y cells following DBDPE exposure and further revealed that DBDPE reduced the binding between TTR and Aβ by competing with the strand G region sites on the TTR/TTR-like protein, ultimately exacerbating Aβ deposition and the risk of AD. In short, our study demonstrated that DBDPE induced locomotion neurotoxicity and potential AD risks through intensifying Aβ deposition by inhibiting TTR/TTR-like proteins, providing reference support for risk management and policy formulation related to DBDPE and similarly structured novel BFRs.

Keywords

• Decabromodiphenyl ethane
• Locomotion neurotoxicity
• Molecular mechanisms
• Transthyretin/transthyretin-like
• Amyloid-beta deposition
• Health risks