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<p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta42 (Aβ42) aggregation, neuroinflammation, and synaptic dysfunction. This study combines computational and experimental approaches to investigate the neuroprotective effects of sodium butyrate (NaB). Differentiated SH-SY5Y neurons were exposed to lipopolysaccharide (LPS) and Aβ₁₋₄₂ to model AD-like conditions, and the potential protective effects of NaB were evaluated. MD simulations indicated that NaB may be associated with destabilization of organized Aβ₄₂ fibrils. Alterations in RMSD, Rg, and SASA values indicated structural instability of Aβ₄₂ fibrils in the presence of NaB. Treatment with NaB (10 and 50 µM) significantly improved cell viability compared to the LPS + Aβ group (<i>p</i> &lt; 0.001) and attenuated apoptosis, as evidenced by reduced expression of <i>Bax</i>, <i>Caspase-3</i>, and <i>FOXO3a</i> (<i>p</i> &lt; 0.0001), alongside upregulation of the anti-apoptotic marker <i>Bcl-2</i> (<i>p</i> &lt; 0.01). Moreover, NaB markedly increased the expression of neuroprotective and antioxidant genes, including <i>BDNF</i>, <i>Nrf2</i>, <i>SIRT1</i>, and <i>CREB</i> (<i>p</i> &lt; 0.001), thereby restoring pathways involved in neuronal survival, oxidative stress defense, and synaptic plasticity. Collectively, these effects mitigated LPS + Aβ-induced cytotoxicity, suggesting that NaB exerts its neuroprotective action through epigenetic regulation of stress-response and plasticity networks. Our findings provide robust evidence supporting sodium butyrate as a promising therapeutic candidate for preventing or slowing AD-related neuronal degeneration and highlight its potential translational relevance for future in vivo and clinical investigations.</p>

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Investigation of the effects of sodium butyrate on SH-SY5Y neurons treated with amyloid beta42 and lipopolysaccharide: A computational and experimental study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Vida Arabhalvaei,
  • Seyedeh Niloufar Rajaei,
  • Mohammad Mehdi Alinaghi,
  • Mehrshad Talebi,
  • Fatemeh Dashti,
  • Seyedeh Fatemeh Abachi,
  • Zahra Khodayar,
  • Arad Ranji Jafroodi,
  • Mohammad Jamalaldin,
  • Mahtab Mehboodi,
  • Mohammad Hasan Maleki,
  • Atefeh Rahimi,
  • Payam Baziyar

摘要

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta42 (Aβ42) aggregation, neuroinflammation, and synaptic dysfunction. This study combines computational and experimental approaches to investigate the neuroprotective effects of sodium butyrate (NaB). Differentiated SH-SY5Y neurons were exposed to lipopolysaccharide (LPS) and Aβ₁₋₄₂ to model AD-like conditions, and the potential protective effects of NaB were evaluated. MD simulations indicated that NaB may be associated with destabilization of organized Aβ₄₂ fibrils. Alterations in RMSD, Rg, and SASA values indicated structural instability of Aβ₄₂ fibrils in the presence of NaB. Treatment with NaB (10 and 50 µM) significantly improved cell viability compared to the LPS + Aβ group (p < 0.001) and attenuated apoptosis, as evidenced by reduced expression of Bax, Caspase-3, and FOXO3a (p < 0.0001), alongside upregulation of the anti-apoptotic marker Bcl-2 (p < 0.01). Moreover, NaB markedly increased the expression of neuroprotective and antioxidant genes, including BDNF, Nrf2, SIRT1, and CREB (p < 0.001), thereby restoring pathways involved in neuronal survival, oxidative stress defense, and synaptic plasticity. Collectively, these effects mitigated LPS + Aβ-induced cytotoxicity, suggesting that NaB exerts its neuroprotective action through epigenetic regulation of stress-response and plasticity networks. Our findings provide robust evidence supporting sodium butyrate as a promising therapeutic candidate for preventing or slowing AD-related neuronal degeneration and highlight its potential translational relevance for future in vivo and clinical investigations.