Scholarlink

<p>Zebrafish (<i>Danio rerio</i>) fin amputation is a widely used model for studying sensory axon degeneration and regeneration. After injury, sensory neuron terminals rapidly degenerate before regenerating. While reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂), are known to promote axon regeneration through epidermal mechanisms, their role in degeneration remains unclear. Here, we identify mitochondrial superoxide and reactive nitrogen species (RNS), specifically peroxynitrite, as key drivers of axon fragmentation. Using AlphaFold and DeepNitro predictive modeling, we identified conserved nitration and nitrosylation sites in NMNAT rather than SARM1, two key drivers of a known axon destruction pathway, suggesting the possibility of a redox-dependent regulatory mechanism. We further explored the role of NADPH in axon degeneration since <i>cyba</i> mutants that do not utilize NADPH to generate ROS display delayed sensory axon degeneration. Pharmacological NADPH treatment significantly reduced amputation-induced sensory axon degeneration while enhancing regeneration. NADPH co-administration also mitigated paclitaxel-induced axon loss and improved the tactile response in a model of chemotherapy-induced peripheral neuropathy. These findings reveal a complex interplay between ROS and RNS in axon degeneration and regeneration, positioning NADPH as a promising therapeutic candidate for oxidative stress-related neurodegeneration.</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

A redox-dependent switch governing sensory axon degeneration and regeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月11日

查看全文
  • Chia-Jung Hsieh,
  • Lauryn M. Lee,
  • Sandra Rieger

摘要

Zebrafish (Danio rerio) fin amputation is a widely used model for studying sensory axon degeneration and regeneration. After injury, sensory neuron terminals rapidly degenerate before regenerating. While reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂), are known to promote axon regeneration through epidermal mechanisms, their role in degeneration remains unclear. Here, we identify mitochondrial superoxide and reactive nitrogen species (RNS), specifically peroxynitrite, as key drivers of axon fragmentation. Using AlphaFold and DeepNitro predictive modeling, we identified conserved nitration and nitrosylation sites in NMNAT rather than SARM1, two key drivers of a known axon destruction pathway, suggesting the possibility of a redox-dependent regulatory mechanism. We further explored the role of NADPH in axon degeneration since cyba mutants that do not utilize NADPH to generate ROS display delayed sensory axon degeneration. Pharmacological NADPH treatment significantly reduced amputation-induced sensory axon degeneration while enhancing regeneration. NADPH co-administration also mitigated paclitaxel-induced axon loss and improved the tactile response in a model of chemotherapy-induced peripheral neuropathy. These findings reveal a complex interplay between ROS and RNS in axon degeneration and regeneration, positioning NADPH as a promising therapeutic candidate for oxidative stress-related neurodegeneration.