Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?

Ritson, Megan; Wheeler-Jones, Caroline P.D.; Stolp, Helen B.

Abstract

Neurological diseases with a neurodegenerative component have been associated with alterations in the cerebrovasculature. At the anatomical level, these are centred around changes in cerebral blood flow and vessel organisation. At the molecular level, there is extensive expression of cellular adhesion molecules and increased release of pro-inflammatory mediators. Together, these has been found to negatively impact blood-brain barrier integrity. Systemic inflammation has been found to accelerate and exacerbate endothelial dysfunction, neuroinflammation and degeneration. Here, we review the role of cerebrovasculature dysfunction in neurodegenerative disease and discuss the potential contribution of intermittent pro-inflammatory systemic disease in causing endothelial pathology, highlighting a possible mechanism that may allow broad-spectrum therapeutic targeting in the future.

Citation

Ritson, M., Wheeler-Jones, C. P., & Stolp, H. B. (2024). Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?. Journal of Neuroimmunology, 391, 578363. https://doi.org/10.1016/j.jneuroim.2024.578363

• Journal Article Type: Article
• Acceptance Date: May 2, 2024
• Online Publication Date: May 13, 2024
• Publication Date: 2024-06
• Deposit Date: May 13, 2024
• Publicly Available Date: May 13, 2024
• Journal: Journal of Neuroimmunology
• Print ISSN: 0165-5728
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 391
• Pages: 578363
• DOI: https://doi.org/10.1016/j.jneuroim.2024.578363
• Keywords: Neurodegeneration; Endothelium; Blood -brain barrier; Inflammation; Cerebrovascular; BLOOD-BRAIN-BARRIER; APPEARING WHITE-MATTER; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; AMYLOID-BETA; ADHESION MOLECULES; OXIDATIVE STRESS; PERMEABIL
• Additional Information: This article is maintained by: Elsevier; Article Title: Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?; Journal Title: Journal of Neuroimmunology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jneuroim.2024.578363; Content Type: article; Copyright: © 2024 The Author(s). Published by Elsevier B.V.