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.
Original language | American English |
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Pages (from-to) | 71-83 |
Number of pages | 13 |
Journal | Free Radical Biology and Medicine |
Volume | 194 |
DOIs | |
State | Published - Jan 2023 |
Bibliographical note
Funding Information:This work was supported by the University of Nottingham UK, UK (JRS) and by US Department of Defense, USA (HA), Israeli Science Foundation, Israel (HA), National Institute of Psychobiology in Israel, Israel (HA), Israeli Council for Higher Education Maof, Israel (HA). We also thank the Satell Family Foundation, USA and Neubauer Family Foundation for their support, USA (HA).
Publisher Copyright:
© 2022 Elsevier Inc.
Keywords
- Alzheimer's disease
- Autism spectrum disorder
- Neurodegeneration
- Neurological disorders
- Nitric oxide
- Nitrosative stress
- Oxidative stress
- Redox signalling