Cuproptosis: New Mechanisms Linking Endothelial Dysfunction to Neurodegenerative Diseases and Therapeutic Prospects
- 1College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Abstract
Cuproptosis is a copper-dependent form of regulated cell death driven by disrupted copper homeostasis and mitochondrial metabolic reprogramming. It is distinct from other cell death pathways and has been increasingly linked to vascular endothelial dysfunction and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This article comprehensively reviews the core molecular mechanisms of cuproptosis and its emerging roles in endothelial dysfunction and neurodegeneration, synthesizing recent findings from cellular, animal, and human studies. Cuproptosis exacerbates vascular pathology by impairing endothelial barrier function, inducing oxidative stress, and promoting inflammation and senescence. In the brain, it drives neurodegeneration both directly—via mitochondrial damage and neuronal loss—and indirectly by interacting with pathological proteins such as amyloid-beta and α-synuclein, creating a vicious cycle of copper dysregulation and protein aggregation. This review provides new insights into the pathophysiology of vascular endothelial dysfunction and neurodegenerative diseases by highlighting the pivotal role of cuproptosis. Understanding how cuproptosis links copper metabolism to cell death pathways opens avenues for identifying novel therapeutic targets. Interventions that restore copper homeostasis or block cuproptosis-specific molecular events may offer promising strategies for treating these devastating diseases.
Related
- The "Invisible Killer” of Neurodegeneration: Mitochondrial Dysfunction in Neurodegenerative Disorders, Mechanisms, Emerging Pathways and Therapeutic Strategies
- Epigenetic Mechanisms in Neurodegenerative Diseases: From Genetic Regulation to Therapeutic Potential
- AAV9 Gene Therapy for Ovarian Dysfunction and Reproductive Aging: Molecular Mechanisms, Therapeutic Targets, and Translational Perspectives
- Primary cilia disruption reprograms extracellular vesicle signaling in endothelial dysfunction and cardiovascular disease
- Plasma Lipids Associated with Endothelial Dysfunction in Patients with Type 2 Diabetes: A Cross-Sectional Study Using Lipidomic Analysis
BibTeX
@article{gu2026cuproptosis,
title = {{Cuproptosis: New Mechanisms Linking Endothelial Dysfunction to Neurodegenerative Diseases and Therapeutic Prospects}},
author = {Tianyi Gu and Xiaoyu Wei and Shengyu Hua},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198765},
url = {https://www.mdpi.com/1422-0067/27/19/8765},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cuproptosis: New Mechanisms Linking Endothelial Dysfunction to Neurodegenerative Diseases and Therapeutic Prospects
AU - Tianyi Gu
AU - Xiaoyu Wei
AU - Shengyu Hua
PY - 2026
DA - 2026/09/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198765
UR - https://www.mdpi.com/1422-0067/27/19/8765
AB - Cuproptosis is a copper-dependent form of regulated cell death driven by disrupted copper homeostasis and mitochondrial metabolic reprogramming. It is distinct from other cell death pathways and has been increasingly linked to vascular endothelial dysfunction and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This article comprehensively reviews the core molecular mechanisms of cuproptosis and its emerging roles in endothelial dysfunction and neurodegeneration, synthesizing recent findings from cellular, animal, and human studies. Cuproptosis exacerbates vascular pathology by impairing endothelial barrier function, inducing oxidative stress, and promoting inflammation and senescence. In the brain, it drives neurodegeneration both directly—via mitochondrial damage and neuronal loss—and indirectly by interacting with pathological proteins such as amyloid-beta and α-synuclein, creating a vicious cycle of copper dysregulation and protein aggregation. This review provides new insights into the pathophysiology of vascular endothelial dysfunction and neurodegenerative diseases by highlighting the pivotal role of cuproptosis. Understanding how cuproptosis links copper metabolism to cell death pathways opens avenues for identifying novel therapeutic targets. Interventions that restore copper homeostasis or block cuproptosis-specific molecular events may offer promising strategies for treating these devastating diseases.
SN - 1422-0067
ER -