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Helmholtz Munich I Daniela Barreto

Vitamin A: A Key to Stopping Ferroptosis and Boosting Neuronal Development

Featured Publication, Molecular Targets and Therapeutics, VIRO,

A better understanding of ferroptosis – an iron-dependent form of cell death – is an essential prerequisite for the treatment of (neuro)degenerative diseases and certain types of cancer. A team of researchers led by Dr. Kamyar Hadian from the Research Unit Signaling and Translation and Dr. Michelle Vincendeau from the Institute of Virology, both at Helmholtz Munich, identified that ferroptosis is harmful for neuronal development. By revealing how vitamin A and antioxidants can counteract ferroptosis, the study offers new insights into optimizing stem-cell-based therapies and underscores the importance of managing vitamin A intake in related research.

Cell death is a crucial process in the functioning of almost all multicellular organisms. It helps to maintain balance in tissues by eliminating damaged or defective cells. There are several regulated mechanisms for cell death, one of which is ferroptosis. This process is triggered by iron-dependent oxidative damage to cellular lipids, which are vital components of cell membranes, ultimately leading to cell death. Ferroptosis plays a role in various degenerative diseases, including neurodegenerative conditions like the Alzheimer’s or Parkinson’s disease. However, the role of ferroptosis in brain development is still not fully understood. In this study, the researchers examined how ferroptosis can disrupt neurogenesis, the process of forming brain cells. Their findings highlight the importance of inhibiting ferroptosis with antioxidants or vitamin A to support healthy brain cell development.

How Vitamin A and Antioxidants Combat Ferroptosis in Early Neurodevelopment

The research team led by Dr. Kamyar Hadian and Dr. Michelle Vincendeau has uncovered a new role for ferroptosis in neuronal development. In the study, now published in Nature Communications, the scientists explored neuronal differentiation under conditions with or without antioxidants. They found that mature neurons could only be generated in the presence of antioxidants. Surprisingly, they discovered that vitamin A could counteract ferroptotic stress and promote neurogenesis. This finding was further validated using physiologically relevant brain organoid models (“mini-brains-in-a-dish”), where inhibiting ferroptosis was essential for the proper organization. The study also revealed that all-trans-retinoic acid, an active metabolite of vitamin A, activates the retinoic acid receptor (RAR), which upregulates key regulators of ferroptosis suppression.

Together, these new findings uncover a key detrimental role of ferroptosis during neurodevelopment. With this insight, researchers can now more effectively regulate ferroptosis in neuronal production for stem-cell-based therapies. Moreover, the results show that managing vitamin A is essential when conducting studies involving ferroptosis-targeted treatments.

 

Original publication

Tschuck et al. (2024): Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development. Nature Communications. DOI: https://www.nature.com/articles/s41467-024-51996-1

About the scientists

Dr. Kamyar Hadian, Deputy Director of the Research Unit "Signaling and Translation" (SAT) and Group Leader "Cell Signaling and Chemical Biology". Contact: kamyar.hadian@helmholtz-munich.de

Dr. Michelle Vincendeau, Deputy Director of the Institute of Virology and Group Leader "Human Endogenous Retroviruses". Contact: michelle.vincendeau@helmholtz-munich.de

 

Funding information
M.V. was funded by the Deutsche Forschungsgemeinschaft (RTG2668 – project number 435874434, Sachbeihilfe – project number 496872373, Sachbeihilfe – project number 498956525, and Sachbeihilfe – project number 497803923)

Porträt Kayar Hadian

Dr. rer. nat. Kamyar Hadian

Deputy Director of the Research Unit Signaling and Translation / Group Leader Cell Signaling and Chemical Biology

Dr. Michelle Vincendeau

Group Leader / Deputy Director of Institute