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

Chen Wang; Lingjun Zeng; Yeyong Li; Chongli Shi; Yi Peng; Ruolin Pan; Mengyan Huang; Susu Wang; Jin Zhang; Hui Li

doi:10.1016/j.envint.2022.107482

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

Environ Int. 2022 Oct:168:107482. doi: 10.1016/j.envint.2022.107482. Epub 2022 Aug 18.

Authors

Chen Wang¹, Lingjun Zeng¹, Yeyong Li¹, Chongli Shi¹, Yi Peng¹, Ruolin Pan¹, Mengyan Huang¹, Susu Wang¹, Jin Zhang¹, Hui Li²

Affiliations

¹ Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
² Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China. Electronic address: huili2018@shu.edu.cn.

PMID: 35998411
DOI: 10.1016/j.envint.2022.107482

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