Scholarlink

<p>Neuroinflammation has been recognized as a central pathological mechanism in Alzheimer’s disease (AD), modulated by diverse molecular pathways. Among these, the tumor necrosis factor superfamily (TNFSF) pathway serves as a pivotal mediator of inflammatory responses in higher organisms, representing a potential therapeutic target for AD treatment. Notably, TNF alpha-induced protein 1 (TNFAIP1) is significantly upregulated following amyloid-beta<sub>1-42</sub> (Aβ<sub>1-42</sub>) accumulation in the postmortem brains of patients with AD and in transgenic <i>Caenorhabditis elegans</i> models. However, the regulatory mechanism of its ortholog F22E5.6 in <i>C. elegans</i> and its role in Aβ neurotoxicity remain elusive due to the absence of the core TNFSF members in this model. Through systematic screening of TNFSF orthologs, the <i>trf-1</i> gene that encodes the adapter protein, TNF receptor-associated factor (TRAF), has been identified as a critical regulator in Aβ<sub>1-42</sub>-induced F22E5.6 overexpression of <i>C. elegans</i>. In this genetic model, the only Toll-like receptor TOL-1 in <i>C. elegans</i> serves as a potential receptor to activate TRF-1 and to transmit this signal to the SRC-2/PMK-3 axis, thereby executing the effects on mitochondrial homeostasis disequilibrium. These findings reveal the regulatory mechanism on Aβ<sub>1-42</sub>-induced F22E5.6/TNFAIP1 overexpression and its involvement in AD model of <i>C. elegans,</i> providing a clue to resolve the paradox of TNFSF-mediated inflammation in organisms lacking the canonical TNFSF pathway.</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

Caenorhabditis Elegans Ortholog of TNF Alpha-Induced Protein 1 is Upregulated by TOL-1 and Exacerbates Amyloid-Beta-Associated Pathology

  • 期刊论文

  • 发表日期：

    2025年11月22日

查看全文
  • Yanmei Su,
  • Donghua Zhang,
  • Yixin Li,
  • Huan Gu,
  • Wenhu Li,
  • Wenhui Zhou,
  • Ninghui Zhao,
  • Xiaowei Huang

摘要

Neuroinflammation has been recognized as a central pathological mechanism in Alzheimer’s disease (AD), modulated by diverse molecular pathways. Among these, the tumor necrosis factor superfamily (TNFSF) pathway serves as a pivotal mediator of inflammatory responses in higher organisms, representing a potential therapeutic target for AD treatment. Notably, TNF alpha-induced protein 1 (TNFAIP1) is significantly upregulated following amyloid-beta1-42 (Aβ1-42) accumulation in the postmortem brains of patients with AD and in transgenic Caenorhabditis elegans models. However, the regulatory mechanism of its ortholog F22E5.6 in C. elegans and its role in Aβ neurotoxicity remain elusive due to the absence of the core TNFSF members in this model. Through systematic screening of TNFSF orthologs, the trf-1 gene that encodes the adapter protein, TNF receptor-associated factor (TRAF), has been identified as a critical regulator in Aβ1-42-induced F22E5.6 overexpression of C. elegans. In this genetic model, the only Toll-like receptor TOL-1 in C. elegans serves as a potential receptor to activate TRF-1 and to transmit this signal to the SRC-2/PMK-3 axis, thereby executing the effects on mitochondrial homeostasis disequilibrium. These findings reveal the regulatory mechanism on Aβ1-42-induced F22E5.6/TNFAIP1 overexpression and its involvement in AD model of C. elegans, providing a clue to resolve the paradox of TNFSF-mediated inflammation in organisms lacking the canonical TNFSF pathway.