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Background <p>Alzheimer’s disease (AD) is characterized by cognitive decline, amyloid-beta (Aβ) accumulation, and tau hyperphosphorylation. Effective therapies remain limited; therefore, recent studies have explored microRNAs as potential therapeutic targets.</p> Methods <p>miR-4536-3p inhibition was investigated using in vitro (SH-SY5Y cells) and in vivo (5xFAD mouse) AD models. Apoptosis, neuronal markers, and signaling pathways were assessed through functional assays. Cognitive effects were evaluated via the Morris water maze.</p> Results <p>miR-4536-3p inhibition increased an expression of Drebrin1 (DBN1), a key regulator of synaptic plasticity, but it reduced Aβ deposition, tau phosphorylation, and apoptosis. The treatment improved neuronal marker levels and significantly enhanced the spatial learning and memory of 5xFAD mice. Mechanistically, miR-4536-3p inhibition activated the PI3K/Akt/GSK3β signaling pathway, suppressing apoptosis and mitigating AD pathology.</p> Conclusion <p>miR-4536-3p inhibition offers a promising therapeutic strategy for AD by restoring the DBN1 expression, reducing neurodegeneration, and improving cognitive outcomes through PI3K/Akt pathway modulation.</p>

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A novel miR-4536-3p inhibition ameliorates Alzheimer’s disease by reducing Aβ accumulation and tau phosphorylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • Jiyun Choi,
  • Dohee Kim,
  • Haewon Jeong,
  • Jinsu Hwang,
  • Mahesh Ramalingam,
  • Sujin Han,
  • Hyong-Ho Cho,
  • Byeong C. Kim,
  • Han-Seong Jeong,
  • Sujeong Jang

摘要

Background

Alzheimer’s disease (AD) is characterized by cognitive decline, amyloid-beta (Aβ) accumulation, and tau hyperphosphorylation. Effective therapies remain limited; therefore, recent studies have explored microRNAs as potential therapeutic targets.

Methods

miR-4536-3p inhibition was investigated using in vitro (SH-SY5Y cells) and in vivo (5xFAD mouse) AD models. Apoptosis, neuronal markers, and signaling pathways were assessed through functional assays. Cognitive effects were evaluated via the Morris water maze.

Results

miR-4536-3p inhibition increased an expression of Drebrin1 (DBN1), a key regulator of synaptic plasticity, but it reduced Aβ deposition, tau phosphorylation, and apoptosis. The treatment improved neuronal marker levels and significantly enhanced the spatial learning and memory of 5xFAD mice. Mechanistically, miR-4536-3p inhibition activated the PI3K/Akt/GSK3β signaling pathway, suppressing apoptosis and mitigating AD pathology.

Conclusion

miR-4536-3p inhibition offers a promising therapeutic strategy for AD by restoring the DBN1 expression, reducing neurodegeneration, and improving cognitive outcomes through PI3K/Akt pathway modulation.