Scholarlink

Excessive generation of reactive oxygen species (ROS), particularly superoxide anion (O2•−), is a central driver of oxidative stress and contributes to cardiovascular and neurodegenerative diseases including hypertension, atherosclerosis, diabetes, and Alzheimer’s disease. The superoxide dismutase (SOD) family—cytosolic copper/zinc (Cu/Zn) SOD (SOD1), mitochondrial manganese (Mn) SOD (SOD2), and extracellular Cu/Zn SOD (SOD3)—forms the first enzymatic defense by converting O2•− to hydrogen peroxide (H2O2). This reaction not only limits peroxynitrite (ONOO−) formation and preserves nitric oxide (NO) bioavailability but also supports compartmentalized redox signaling critical for vascular tone, angiogenesis, and neuronal function. SOD activity is tightly governed by metal cofactors: Cu delivery to SOD1 and SOD3 requires coordinated action of Cu transporters and chaperones such as CTR1, CCS, Atox1, and ATP7A, while Mn incorporation is essential for SOD2. Dysregulation of these pathways leads to endothelial dysfunction, vascular remodeling, and neuronal injury. This chapter summarizes the biochemical properties of each SOD isoform, their Cu-dependent regulation, and their roles in cardiovascular and neurovascular pathology. We also highlight therapeutic strategies using SOD mimetics, gene therapy, and exercise-induced antioxidant adaptation, emphasizing how precise targeting of SODs and copper trafficking systems may translate into effective interventions for oxidative stress–driven diseases.

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

Superoxide Dismutases as Redox Regulators and Therapeutic Targets in Vascular and Neurodegenerative Disease

  • 章节

  • 发表日期：

    2026年

查看全文
  • Tohru Fukai,
  • Varadarajan Sudhahar,
  • Masuko Ushio-Fukai

摘要

Excessive generation of reactive oxygen species (ROS), particularly superoxide anion (O2•−), is a central driver of oxidative stress and contributes to cardiovascular and neurodegenerative diseases including hypertension, atherosclerosis, diabetes, and Alzheimer’s disease. The superoxide dismutase (SOD) family—cytosolic copper/zinc (Cu/Zn) SOD (SOD1), mitochondrial manganese (Mn) SOD (SOD2), and extracellular Cu/Zn SOD (SOD3)—forms the first enzymatic defense by converting O2•− to hydrogen peroxide (H2O2). This reaction not only limits peroxynitrite (ONOO−) formation and preserves nitric oxide (NO) bioavailability but also supports compartmentalized redox signaling critical for vascular tone, angiogenesis, and neuronal function. SOD activity is tightly governed by metal cofactors: Cu delivery to SOD1 and SOD3 requires coordinated action of Cu transporters and chaperones such as CTR1, CCS, Atox1, and ATP7A, while Mn incorporation is essential for SOD2. Dysregulation of these pathways leads to endothelial dysfunction, vascular remodeling, and neuronal injury. This chapter summarizes the biochemical properties of each SOD isoform, their Cu-dependent regulation, and their roles in cardiovascular and neurovascular pathology. We also highlight therapeutic strategies using SOD mimetics, gene therapy, and exercise-induced antioxidant adaptation, emphasizing how precise targeting of SODs and copper trafficking systems may translate into effective interventions for oxidative stress–driven diseases.