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<p>Aluminum, a ubiquitous environmental neurotoxin, has been implicated in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD). While Aβ deposition is a hallmark of AD progression, the molecular mechanisms underlying aluminum-induced Aβ aggregation remain incompletely understood. This study examines the role of the ciRs-7–miR-7–UBE2A axis in aluminum-induced Aβ deposition. Healthy male SD rats and PC12 cells were stratified into groups based on aluminum maltolate exposure levels to establish an in vivo and in vitro neurotoxicity model. Hippocampal aluminum content, along with the expression levels of ciRs-7, miR-7, UBE2A, and Aβ1-42, were systematically analyzed. The results demonstrated a dose-dependent decrease in ciRs-7 and UBE2A expression with escalating aluminum exposure, accompanied by concurrent upregulation of miR-7 and Aβ1-42 accumulation. Conversely, ciRs-7 overexpression reversed these pathological trends. Mechanistically, aluminum exposure downregulates ciRs-7 in the hippocampus, thereby derepressing miR-7 activity, which suppresses UBE2A expression and ultimately promotes Aβ deposition. These results identify a novel circRNA-dependent mechanism in aluminum neurotoxicity, suggesting therapeutic targets for AD intervention.</p>

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Aluminum Exposure Leads to Aβ Deposition via the ciRs-7 Pathway

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Lei Zhang,
  • Yonghao Ma,
  • Hailun Fang,
  • Yujuan Gong,
  • Chenyang Li,
  • Huaxing Meng,
  • Jing Song,
  • Xiaoting Lu,
  • Huifang Zhang,
  • Qiao Niu,
  • Linping Wang

摘要

Aluminum, a ubiquitous environmental neurotoxin, has been implicated in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD). While Aβ deposition is a hallmark of AD progression, the molecular mechanisms underlying aluminum-induced Aβ aggregation remain incompletely understood. This study examines the role of the ciRs-7–miR-7–UBE2A axis in aluminum-induced Aβ deposition. Healthy male SD rats and PC12 cells were stratified into groups based on aluminum maltolate exposure levels to establish an in vivo and in vitro neurotoxicity model. Hippocampal aluminum content, along with the expression levels of ciRs-7, miR-7, UBE2A, and Aβ1-42, were systematically analyzed. The results demonstrated a dose-dependent decrease in ciRs-7 and UBE2A expression with escalating aluminum exposure, accompanied by concurrent upregulation of miR-7 and Aβ1-42 accumulation. Conversely, ciRs-7 overexpression reversed these pathological trends. Mechanistically, aluminum exposure downregulates ciRs-7 in the hippocampus, thereby derepressing miR-7 activity, which suppresses UBE2A expression and ultimately promotes Aβ deposition. These results identify a novel circRNA-dependent mechanism in aluminum neurotoxicity, suggesting therapeutic targets for AD intervention.