Nawab John Dar ¹ David Soriano Castell ¹ David Soriano Castell ² Pamela Maher ^1*

• ¹ Salk Institute for Biological Studies, La Jolla, United States
• ² Aligarh Muslim University, Aligarh, Uttar Pradesh, India

mechanisms underlying this process are remarkably similar, if not identical, to the cell death process named ferroptosis some years later, when the involvement of iron-dependent lipid peroxidation was first described, and both pathways are currently thought to be one and the same process. Oxytosis/ferroptosis has emerged as a potential key factor in the progression of neurodegenerative diseases, linking various mechanisms such as oxidative stress, mitochondrial dysfunction, and immune dysregulation, and it likely plays an important role in these interconnected pathways, making it a promising target for therapeutic innovation. Recent studies have illuminated the roles of ferroptosis-related genes and molecular mechanisms in the development of Alzheimer's disease (AD) and Parkinson's disease (PD), offering potential avenues for intervention. This editorial presents four significant studies that explore the relationship between ferroptosis, immune system infiltration, and mitochondrial health in the context of neurodegenerative diseases.Zhao et al. investigated the link between ferroptosis and AD using a robust bioinformatics approach. By analyzing datasets from the Gene Expression Omnibus (GEO) and leveraging the FerrDb database, they identified 18 differentially expressed ferroptosis-related hub genes. A machine learning-based diagnostic model using the random forest algorithm demonstrated strong predictive accuracy, with an area under the curve (AUC) of 0.824 in the training set and 0.734 in the validation set. Additionally, Zhao et al. uncovered significant alterations in the immune microenvironment of AD patients, such as increased CD4+ T resting memory cells, M2 macrophages, and neutrophils. Notable correlations were identified between ferroptosis-related hub genes and immune cells, with DDIT4 strongly linked to CD4+ T memory resting cells and AKR1C2 positively correlated with M2 macrophages. These findings not only implicate ferroptosis in AD progression but also suggest its potential as a biomarker for diagnosis.Therapeutic targets were identified by integrating microRNA (miRNA) and drug interaction analyses, with DDIT4 emerging as a promising candidate for modulating immune responses. This study highlights the intricate relationship between ferroptosis, immune dysregulation, and AD pathology, laying a foundation for future targeted therapies. In conclusion, the exploration of oxytosis/ferroptosis in neurodegenerative diseases has opened new avenues for understanding and potentially treating these complex conditions. The intricate interplay between ferroptosis, immune responses, and mitochondrial health highlights the multifaceted nature of neurodegeneration. As research progresses, the identification of ferroptosisrelated biomarkers and therapeutic targets holds promise for developing precision medicine approaches that could significantly improve patient outcomes. Future studies should continue to unravel the regulatory networks and molecular mechanisms underlying ferroptosis, paving the way for innovative treatments that address the root causes of neurodegenerative diseases. By advancing our knowledge in this field, we move closer to mitigating the devastating impact of diseases like AD and PD, ultimately enhancing the quality of life for millions in an increasingly aged population.