Oxidative Stress-Induced mechanisms in neurodegeneration and Eryptosis: Implications for neurological and systemic disorders

Abstract

The significant association between development of neurological diseases, like Alzheimer’s, Parkinson’s or depression and oxidative stress occurs from disturbance in the balance between oxidative and antioxidative processes due to chronic stress. Unlike previous reviews that focused only on neurological or systemic diseases, this review discusses the mechanisms that connect oxidative stress and neuroinflammation or eryptosis in both neurological, neurodegenerative, and various systemic diseases, clarifying two completely distinct mechanisms of response to oxidative stress that are common to multiple clinical conditions. This review explores the complex involvement of oxidative damage in neurodegeneration and explains its contribution to inflammation, protein aggregation, and disruption of cellular functions. Crucial components in this process are reactive oxygen and reactive nitrogen species, which can be generated both endogenously or exogenously. Primary sources of ROS in cells are NADPH oxidases, mitochondria, xanthine oxidase and growth factor receptors. Elevated ROS levels disrupt cellular homeostasis and cause oxidative damage and inflammatory responses in neurological disorders characterised by the activation of microglia, astrocytes, and infiltrating CD4 + T cells. Similarly, in systemic disease, this disruption happens through eryptosis. In addition, chronic stress damages antioxidant defence, which further worsens pathological processes. A deeper understanding of the underlying mechanisms provides novel insights into therapeutic strategies for reducing the effects of oxidative stress in both neurological and systemic diseases.