Early-life and chronic exposure to di(2-ethylhexyl) phthalate enhances amyloid-β toxicity associated with an autophagy-related gene in Caenorhabditis elegans Alzheimer's disease models

Abstract

The widespread use of di(2-ethylhexyl) phthalate (DEHP) has resulted in its ubiquitous presence in the environment, which has led to serious health concerns. One of these concerns is its possible link to Alzheimer's disease (AD), which is the most common neurodegenerative disease in aged individuals. This study investigated whether early-life and chronic exposure to DEHP affects AD via the toxicity of amyloid-β (Aβ), which has been implicated in the pathogenesis of AD, using Caenorhabditis elegans AD models (strains CL4176 and CL2006). We show that early-life DEHP exposure increased Aβ toxicity in C. elegans strains CL4176 and CL2006. Early-life and chronic exposure to DEHP also significantly increased intracellular ROS levels and Aβ deposition in aged CL2006 nematodes. Moreover, it was found that DEHP-induced Aβ toxicity does not require transcription factors DAF-16 or SKN-1, while early-life and chronic exposure to DEHP significantly increased the accumulation of lysosome-related organelles and the mRNA levels of the autophagy-related gene bec-1 in aged CL2006 nematodes. Our findings suggest that early-life and chronic exposure to DEHP enhances Aβ toxicity, which may be associated with the autophagy-lysosomal degradation pathway in C. elegans.

Keywords: Alzheimer’s disease; Amyloid-β; Autophagy; C. elegans; DEHP; Lysosome.