Scholarlink

<p>Secondary neuronal death following traumatic brain injury (TBI) constitutes a central pathological mechanism driving permanent functional deficits. Mounting evidence reveals the “autophagy-ferroptosis axis,” forged by dysfunctional autophagy converging with activated ferroptosis, as a critical driver of this process. This review synthesizes current evidence on the molecular underpinnings of this axis within TBI, suggesting the AMPK (AMP-activated protein kinase)-BECN1 (beclin 1)-System Xc⁻ pathway as one potential core regulatory network. We provide an in-depth exploration of how this network may orchestrate neuronal fate through the “upstream decision-making” of the energy sensor AMPK, the “dual-function bridge” role of BECN1, and the “terminal executioner” function of System Xc⁻. Building upon this foundation, the review further advances an intervention hypothesis leveraging exosomes derived from olfactory ensheathing cells overexpressing brain-derived neurotrophic factor (BDNF-OE-OEC-Exos). We suggest their potential for TBI therapy, while acknowledging that this concept remains to be validated in relevant disease models and human studies.</p> Graphical Abstract <p></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

The AMPK-BECN1-System Xc⁻ Pathway in Traumatic Brain Injury: Implications for Exosome-Based Therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月19日

查看全文
  • Shenglin Yan,
  • Weican Chen,
  • Yuxin Huang,
  • Nanying Jiang,
  • Yibin Liu,
  • Weifeng Liu

摘要

Secondary neuronal death following traumatic brain injury (TBI) constitutes a central pathological mechanism driving permanent functional deficits. Mounting evidence reveals the “autophagy-ferroptosis axis,” forged by dysfunctional autophagy converging with activated ferroptosis, as a critical driver of this process. This review synthesizes current evidence on the molecular underpinnings of this axis within TBI, suggesting the AMPK (AMP-activated protein kinase)-BECN1 (beclin 1)-System Xc⁻ pathway as one potential core regulatory network. We provide an in-depth exploration of how this network may orchestrate neuronal fate through the “upstream decision-making” of the energy sensor AMPK, the “dual-function bridge” role of BECN1, and the “terminal executioner” function of System Xc⁻. Building upon this foundation, the review further advances an intervention hypothesis leveraging exosomes derived from olfactory ensheathing cells overexpressing brain-derived neurotrophic factor (BDNF-OE-OEC-Exos). We suggest their potential for TBI therapy, while acknowledging that this concept remains to be validated in relevant disease models and human studies.

Graphical Abstract