Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia

Vascular dementia (VaD) is a neurodegenerative disorder characterized by chronic oxygen insufficiency, leading to the generation of oxygen-free radicals, inflammatory responses, disturbances in iron metabolism, lipid peroxidation, and other pathological changes that disrupt intracellular homeostasis...

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Main Authors: Xin-yi Zou, Luo-yang Cai, Jin Zhang, Ying Yuan, Jie Song, Zhao-duan Hu, Xiao-feng Ruan, Rui Peng, Xiao-ming Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2025.1585079/full
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author Xin-yi Zou
Luo-yang Cai
Jin Zhang
Ying Yuan
Jie Song
Jie Song
Zhao-duan Hu
Zhao-duan Hu
Zhao-duan Hu
Xiao-feng Ruan
Xiao-feng Ruan
Rui Peng
Rui Peng
Rui Peng
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
author_facet Xin-yi Zou
Luo-yang Cai
Jin Zhang
Ying Yuan
Jie Song
Jie Song
Zhao-duan Hu
Zhao-duan Hu
Zhao-duan Hu
Xiao-feng Ruan
Xiao-feng Ruan
Rui Peng
Rui Peng
Rui Peng
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
author_sort Xin-yi Zou
collection DOAJ
description Vascular dementia (VaD) is a neurodegenerative disorder characterized by chronic oxygen insufficiency, leading to the generation of oxygen-free radicals, inflammatory responses, disturbances in iron metabolism, lipid peroxidation, and other pathological changes that disrupt intracellular homeostasis. These processes ultimately lead to neuronal death and cognitive dysfunction. Normal neurological functions depend on the capacity of the iron homeostatic system to regulate the balance of oxidative states. Imbalances in iron metabolism render nerve cells highly susceptible to cell death induced by iron accumulation. Ferroptosis is a process in which iron catalyzes the peroxidation of unsaturated fatty acid-rich lipids, with ferrous iron or lipoxygenase acting as catalysts and ultimately resulting in cellular demise. Heme oxygenase-1 (HO-1) is a critical enzyme involved in the cellular response to oxidative stress and is essential for regulating signaling pathways linked to iron-mediated cell death. It protects neuronal cells by mitigating oxidative stress, reducing inflammation, and enhancing mitochondrial function, thereby alleviating cerebrovascular injury and slowing the progression of VaD. This paper provides a theoretical framework for understanding and potentially treating VaD-related neuronal injury through the investigation of ferroptosis mechanisms, the biological functions of HO-1, and its role in regulating ferroptosis.
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spelling doaj-art-bcc3b5e4822d47a4aeb2255605f994bc2025-08-20T02:24:14ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-06-011810.3389/fnmol.2025.15850791585079Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementiaXin-yi Zou0Luo-yang Cai1Jin Zhang2Ying Yuan3Jie Song4Jie Song5Zhao-duan Hu6Zhao-duan Hu7Zhao-duan Hu8Xiao-feng Ruan9Xiao-feng Ruan10Rui Peng11Rui Peng12Rui Peng13Xiao-ming Zhang14Xiao-ming Zhang15Xiao-ming Zhang16Xiao-ming Zhang17College of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaSub-Health Institute, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaSub-Health Institute, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Wuhan, ChinaSub-Health Institute, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, ChinaVascular dementia (VaD) is a neurodegenerative disorder characterized by chronic oxygen insufficiency, leading to the generation of oxygen-free radicals, inflammatory responses, disturbances in iron metabolism, lipid peroxidation, and other pathological changes that disrupt intracellular homeostasis. These processes ultimately lead to neuronal death and cognitive dysfunction. Normal neurological functions depend on the capacity of the iron homeostatic system to regulate the balance of oxidative states. Imbalances in iron metabolism render nerve cells highly susceptible to cell death induced by iron accumulation. Ferroptosis is a process in which iron catalyzes the peroxidation of unsaturated fatty acid-rich lipids, with ferrous iron or lipoxygenase acting as catalysts and ultimately resulting in cellular demise. Heme oxygenase-1 (HO-1) is a critical enzyme involved in the cellular response to oxidative stress and is essential for regulating signaling pathways linked to iron-mediated cell death. It protects neuronal cells by mitigating oxidative stress, reducing inflammation, and enhancing mitochondrial function, thereby alleviating cerebrovascular injury and slowing the progression of VaD. This paper provides a theoretical framework for understanding and potentially treating VaD-related neuronal injury through the investigation of ferroptosis mechanisms, the biological functions of HO-1, and its role in regulating ferroptosis.https://www.frontiersin.org/articles/10.3389/fnmol.2025.1585079/fullheme oxygenase 1ferroptosisvascular dementiaoxidative stresslipid peroxidation
spellingShingle Xin-yi Zou
Luo-yang Cai
Jin Zhang
Ying Yuan
Jie Song
Jie Song
Zhao-duan Hu
Zhao-duan Hu
Zhao-duan Hu
Xiao-feng Ruan
Xiao-feng Ruan
Rui Peng
Rui Peng
Rui Peng
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
Xiao-ming Zhang
Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
Frontiers in Molecular Neuroscience
heme oxygenase 1
ferroptosis
vascular dementia
oxidative stress
lipid peroxidation
title Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
title_full Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
title_fullStr Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
title_full_unstemmed Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
title_short Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia
title_sort mechanism of heme oxygenase 1 regulation of ferroptosis in vascular dementia
topic heme oxygenase 1
ferroptosis
vascular dementia
oxidative stress
lipid peroxidation
url https://www.frontiersin.org/articles/10.3389/fnmol.2025.1585079/full
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