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Ferroptosis at the crossroads: Insights and advances in non-neoplastic pancreatic diseases.

Duolun Gao¹, Tingting Chen², Jize Dong¹

¹Department of Gastroenterology, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People's Republic of China; Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People's Republic of China.

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|May 18, 2025

Summary

Ferroptosis, a cell death form involving iron and lipid peroxidation, is linked to pancreatic diseases. This review explores ferroptosis mechanisms and its therapeutic potential for pancreatitis and diabetes.

Keywords:

Diabetes mellitus Ferroptosis GPX4 Lipid peroxidation Non-neoplastic diseases Pancreatitis

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Area of Science:

Cellular Biology
Biochemistry
Pathology

Background:

Ferroptosis is a regulated cell death marked by iron accumulation and lipid peroxidation.
It is counteracted by antioxidants like glutathione (GSH) and glutathione peroxidase 4 (GPX4).
Ferroptosis is implicated in pancreatic disorders, including pancreatitis and diabetes mellitus.

Purpose of the Study:

To review ferroptosis mechanisms, focusing on iron overload, lipid peroxidation, and regulatory molecules.
To examine the role of ferroptosis in non-neoplastic pancreatic diseases.
To identify novel therapeutic agents targeting ferroptosis for pancreatic conditions.

Main Methods:

Literature review of ferroptosis mechanisms and pathways.
Analysis of the system xc-/GSH/GPX4 axis in ferroptosis.
Investigation of ferroptosis's role in pancreatitis and diabetes.

Main Results:

Ferroptosis is modulated by iron, lipid peroxidation, and specific molecular pathways.
The p53 tumor suppressor and transcription factors 3/4 influence ferroptosis.
Ferroptosis plays a role in the pathogenesis of pancreatitis and diabetes.

Conclusions:

Understanding ferroptosis mechanisms is crucial for pancreatic disease research.
Targeting ferroptosis offers potential therapeutic strategies for pancreatitis and diabetes.
Further research into ferroptosis modulators may lead to novel treatments for pancreatic disorders.