Nitric oxide-mediated neuroinflammatory pathways as treatment targets in neurodegeneration

Cale, Jennifer; Farr, Tracy D.; Serres, Sébastien; Steinert, Joern R.

Abstract

Vascular insufficiency associated with a dysfunctional neurovascular unit (NVU) develops over years without obvious clinical symptoms and can be exacerbated by environmental stress or lifestyle choices. Astrocytic responses to endothelial malfunction that arises from a vascular insufficiency include the release of signaling molecules such as nitric oxide (NO) which is involved in a bidirectional communication between vascular tissues, astrocytes, and neurons. These NO-mediated signals are required for physiological responses to neuronal activity to signal to the vascular bed and conversely, endothelial-derived NO communicates with perivascular astrocytes. Following vascular damage, these communication routes become dysfunctional and may result in neurotoxicity associated with enhanced oxidative and nitrergic stress impacting on astrocyte-mediated regulation of neurovascular coupling. The underlying signaling is subject to ongoing research to uncover targets for therapeutic interventions with focus on the NO and redox-mediated insults within the NVU.

Collectively, the processes have a significant impact on physiological and pathological brain function and undergo changes with age which poses an enhanced risk for aggravating neurovascular diseases and neurodegeneration.

Citation

Cale, J., Farr, T. D., Serres, S., & Steinert, J. R. (2025). Nitric oxide-mediated neuroinflammatory pathways as treatment targets in neurodegeneration. In Therapeutic Applications of Nitric Oxide in Cancer and Inflammatory Disorders (79-96). Elsevier. https://doi.org/10.1016/b978-0-443-22354-9.00005-x

• Publication Date: 2025
• Deposit Date: Feb 25, 2025
• Pages: 79-96
• Book Title: Therapeutic Applications of Nitric Oxide in Cancer and Inflammatory Disorders
• Chapter Number: 5
• ISBN: 9780443223549
• DOI: https://doi.org/10.1016/b978-0-443-22354-9.00005-x
• Public URL: https://nottingham-repository.worktribe.com/output/45854185
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/B978044322354900005X