Universität zu Köln

Shi, Xin (2024). Targeting NOX2 to combat oxidative stress and neuroinflammation and provide neuroprotection in neurodegeneration. PhD thesis, Universität zu Köln.

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Abstract

The imbalance between antioxidants and free radicals/reactive oxygen species (ROS) characterizes oxidative stress (OS), which induces biological responses and is linked to diseases in the central nervous system (CNS). NADPH oxidase (NOX) fulfills a critical function in producing endothelial ROS, compromising the blood-retinal barrier and depleting retinal ganglion cells (RGCs) and degeneration associated with glaucoma. Inhibition of NOX2 markedly diminishes oxidative stress, immune dysregulation, and damage to the internal blood-retinal barrier (iBRB) and the neurovascular unit, safeguarding against RGC loss and optic nerve deterioration in glaucoma models. The study revealed that NOX2-derived ROS facilitates pro-inflammatory signaling via endothelin-1 (ET-1), activating the ERK1/2 signaling pathway and shifting microglia toward a pro-inflammatory M1 phenotype. Consequently, NOX2 is identified as a critical target for neuroprotective treatments in glaucoma, with its inhibition offering protection against damage to the iBRB and neurovascular unit and mitigating RGC loss and optic nerve degeneration.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Shi, Xin shixinsx123@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-736721
Date:	2024
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language NADPH oxidase, NOX2, Oxidative stress, Reactive oxygen species, Neuroinflammation, Neurodegeneration English
Date of oral exam:	16 August 2024
Referee:	Name Academic Title Prokosch, V. Universitätsprofessorin Dr. med. Utermöhlen, O. Universitätsprofessor Dr. med.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/73672