Scholarlink

<p>Reelin signaling regulates multiple pathways in neurodegenerative conditions, including neuronal migration, synaptic plasticity, tau phosphorylation, and amyloidogenic processing of amyloid precursor protein (APP). This study aimed to investigate the impact of reelin downregulation on the expression of topoisomerase IIβ (topo IIβ), given its crucial role in neuronal differentiation and its established association with neurodegenerative disorders such as Alzheimer’s disease (AD). Furthermore, we sought to elucidate the potential relationship between reelin downregulation and proteins implicated in the pathophysiology of AD. Firstly, the optimum concentration of small interfering RNAs (siRNA) targeting <i>reelin</i> was transfected into SH-SY5Y cells using Lipofectamine RNAiMAX reagent. The downregulation of <i>reelin</i> was confirmed at the mRNA level by real-time quantitative polymerase chain reaction (qRT-PCR). <i>Reelin</i>-mediated molecular alterations at both the mRNA and protein levels were analyzed by qRT-PCR and Western blotting. <i>Reelin</i> downregulation led to a decrease in the number of viable cells as determined by the MTT assay. Consistent with the downregulation of <i>reelin</i> gene expression, <i>topo IIβ, Psen1,</i> and <i>BACE1</i> expressions were also reduced, whereas <i>tau</i> and <i>APP</i> expressions were upregulated. Although siRNA treatment effectively decreased <i>reelin</i> mRNA levels and the proteolytic fragment of reelin protein, no significant change was observed in total full-length reelin protein levels, suggesting the involvement of post-transcriptional regulatory mechanisms. Moreover, pTAU and APP protein expressions were increased, while Nurr1 protein was decreased in <i>reelin</i>-silenced cells. These findings suggest that downregulation of <i>reelin</i> gene expression may contribute to neurodegeneration through alterations in <i>topo IIβ</i> and <i>nurr1</i> expression, in addition to changes in proteins associated with AD pathology.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular links between reelin downregulation, topoisomerase IIβ alterations, and proteins involved in Alzheimer pathology in human SH-SY5Y neuroblastoma cell line

  • 期刊论文

  • 发表日期：

    2026年6月30日

查看全文
  • Sule Terzioglu-Usak,
  • Merve Zaim,
  • Merve Beker,
  • Sevim Isik,
  • Birsen Elibol

摘要

Reelin signaling regulates multiple pathways in neurodegenerative conditions, including neuronal migration, synaptic plasticity, tau phosphorylation, and amyloidogenic processing of amyloid precursor protein (APP). This study aimed to investigate the impact of reelin downregulation on the expression of topoisomerase IIβ (topo IIβ), given its crucial role in neuronal differentiation and its established association with neurodegenerative disorders such as Alzheimer’s disease (AD). Furthermore, we sought to elucidate the potential relationship between reelin downregulation and proteins implicated in the pathophysiology of AD. Firstly, the optimum concentration of small interfering RNAs (siRNA) targeting reelin was transfected into SH-SY5Y cells using Lipofectamine RNAiMAX reagent. The downregulation of reelin was confirmed at the mRNA level by real-time quantitative polymerase chain reaction (qRT-PCR). Reelin-mediated molecular alterations at both the mRNA and protein levels were analyzed by qRT-PCR and Western blotting. Reelin downregulation led to a decrease in the number of viable cells as determined by the MTT assay. Consistent with the downregulation of reelin gene expression, topo IIβ, Psen1, and BACE1 expressions were also reduced, whereas tau and APP expressions were upregulated. Although siRNA treatment effectively decreased reelin mRNA levels and the proteolytic fragment of reelin protein, no significant change was observed in total full-length reelin protein levels, suggesting the involvement of post-transcriptional regulatory mechanisms. Moreover, pTAU and APP protein expressions were increased, while Nurr1 protein was decreased in reelin-silenced cells. These findings suggest that downregulation of reelin gene expression may contribute to neurodegeneration through alterations in topo IIβ and nurr1 expression, in addition to changes in proteins associated with AD pathology.