The contribution of an imbalanced redox signalling to neurological and neurodegenerative conditions

Steinert, Joern R.; Amal, Haitham

Abstract

Nitric oxide and other redox active molecules such as oxygen free radicals provide essential signalling in diverse neuronal functions, but their excess production and insufficient scavenging induces cytotoxic redox stress which is associated with numerous neurodegenerative and neurological conditions. A further component of redox signalling is mediated by a homeostatic regulation of divalent metal ions, the imbalance of which contributes to neuronal dysfunction. Additional antioxidant molecules such as glutathione and enzymes such as super oxide dismutase are involved in maintaining a physiological redox status within neurons. When cellular processes are perturbed and generation of free radicals overwhelms the antioxidants capacity of the neurons, a resulting redox damage leads to neuronal dysfunction and cell death. Cellular sources for production of redox-active molecules may include NADPH oxidases, mitochondria, cytochrome P450 and nitric oxide (NO)-generating enzymes, such as endothelial, neuronal and inducible NO synthases. Several neurodegenerative and developmental neurological conditions are associated with an imbalanced redox state as a result of neuroinflammatory processes leading to nitrosative and oxidative stress. Ongoing research aims at understanding the causes and consequences of such imbalanced redox homeostasis and its role in neuronal dysfunction.

Citation

Steinert, J. R., & Amal, H. (2023). The contribution of an imbalanced redox signalling to neurological and neurodegenerative conditions. Free Radical Biology and Medicine, 194, 71-83. https://doi.org/10.1016/j.freeradbiomed.2022.11.035

• Journal Article Type: Review
• Acceptance Date: Nov 22, 2022
• Online Publication Date: Nov 24, 2022
• Publication Date: 2023-01
• Deposit Date: Nov 25, 2022
• Publicly Available Date: Nov 25, 2023
• Journal: Free Radical Biology and Medicine
• Print ISSN: 0891-5849
• Electronic ISSN: 1873-4596
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 194
• Pages: 71-83
• DOI: https://doi.org/10.1016/j.freeradbiomed.2022.11.035
• Keywords: Physiology (medical); Biochemistry
• Public URL: https://nottingham-repository.worktribe.com/output/14040662
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0891584922009984?via%3Dihub