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

• Published in: Free radical biology & medicine 2023-01, Vol.194, p.71-83
• Main Authors: Steinert, Joern R., Amal, Haitham
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Antioxidants - metabolism; Autism spectrum disorder; Free Radicals - metabolism; Humans; Neurodegeneration; Neurodegenerative Diseases; Neurological disorders; Nitric Oxide; Nitrosative stress; Oxidation-Reduction; Oxidative stress; Oxidative Stress - physiology; Reactive Oxygen Species - metabolism; Redox signalling
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.11.035

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. [Display omitted] •Nitric oxide and other redox active molecules provide essential signalling in neuronal signalling.•Imbalanced redox state as a result of neuroinflammation induces nitrosative and oxidative stress.•Redox stress is associated with neurodegenerative and neurological conditions.