Protective effect and therapeutic significance of glutathione peroxidase 4 in Alzheimer's disease
Alzheimer's disease (AD) is an age-related neurodegenerative disease with complex and diverse pathogenesis and a lack of effective treatments.
In recent years, oxidative stress has been involved in the pathogenesis of Alzheimer's disease, which has received extensive attention.
glutathione peroxidase 4 (GPx4), as a member of the antioxidase family containing selenium, can reduce esterifying phospholipid hydroperoxide and play an important role in maintaining the REDOX balance of cells.
Especially with the development of iron death research, glutathione peroxidase 4, as a key regulator of iron death, plays an important role in inhibiting lipid peroxidation.
The role of glutathione peroxidase 4 in the pathological mechanism of Alzheimer's disease and the research progress of targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease need to be further summarized.
In a review published in the Chinese Neuroregeneration Research (English Edition) in issue 3, 2025, the team of Professor Sun Li of Jilin University first outlined the gene structure, biological function and regulatory mechanism of glutathione peroxidase 4, and then discussed the important role of glutathione peroxidase 4 in the pathological events closely related to Alzheimer's disease.
Finally, the small molecule drugs, natural plant products and non-drug therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease were summarized.
The team from Professor Li Sun believes that glutathione peroxidase 4 is reduced in Alzheimer's disease brain expression, and related indicators such as oxidative stress, inflammation, iron death and apoptosis are elevated.
A large number of in vivo and in vitro studies have also confirmed that the level of glutathione peroxidase 4 is significantly reduced in the pathological model of Alzheimer's disease, and promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity improve the pathological damage and cognitive function of Alzheimer's disease.
Glutathione peroxidase 4 May be a key target for the treatment of Alzheimer's disease.
The expression of glutathione peroxidase 4 is regulated by a variety of mechanisms. Although we have understood the structure of glutathione peroxidase 4 gene, the regulatory mechanisms of its epigenetic, post-transcriptional and post-translational modifications are still lacking in the study of Alzheimer's disease and need to be further explored in the future.
A variety of small molecule drugs, natural plant products and non-pharmaceutical interventions that may target glutathione peroxidase 4 have shown promising potential in the treatment of Alzheimer's disease.
At present, most studies mainly rely on animal models and lack relevant clinical studies, so clinical trials need to be put into the future to verify the therapeutic effect of targeting glutathione peroxidase 4 in Alzheimer's patients.
Citation:
Shen Y, Zhang G, Wei C, Zhao P, Wang Y, Li M, Sun L (2025) Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer’s disease. Neural Regen Res 20(3):613-631.
