Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Abstract

Aluminum (Al) is a neurotoxic substance associated with cognitive dysfunction and neurodegenerative diseases, such as Alzheimer's disease, but the mechanisms for aluminum neurotoxicity remain to be identi ed. In this work, we try to investigate a novel potential biomarker of cognitive dysfunction following aluminum exposure and the mechanism involved. Recently, miR-134-3p was reported as a novel regulator of cognitive function. To address this, we investigate the expression level of miR-134-3p in plasma from 280 aluminum factory workers and analyzed the correlation between miRNA-134-3p, blood Al concentration, and Montreal Cognitive Assessment Scale (MoCA scale) score. The results implied that occupational aluminum exposure elevated miR-134-3p expression in the plasma of workers accompanied by cognitive impairment. Our experiment studies using both animal models and PC12 cells validated the up-regulation of miR-134-3p caused by aluminum. In addition, we identi ed that palmitoylation enzyme zDHHC3 was the target of miR-134-3p, and the decreasing AMPAR receptors (AMPARs) tra cking was related to the learning and memory impairment induced by aluminum. More importantly, using transfection and interference approaches in PC12 cells, inhibition of miR-134-3p resulted in a recovery of zDHHC3-AMPARs axis to a certain extent in response to aluminum. In summary, miR-134-3p was found to be involved in aluminum neurotoxicity by targeting zDHHC3-AMPARs axis and could serve as a potential biomarker or helpful target.

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

“…It was also found that zDHHC3 is a target of miR-134-3p. miR-134-3p is involved in aluminum neurotoxicity by targeting the zDHHC3-AMPARs axis, which could serve as a potential biomarker or useful target ( Song et al, 2023 ).…”