Pharmacological intervention in oxidative stress as a therapeutic target in neurological disorders

Abstract

Objectives Oxidative stress is a major cellular burden that triggers reactive oxygen species (ROS) and antioxidants that modulate signalling mechanisms. Byproducts generated from this process govern the brain pathology and functions in various neurological diseases. As oxidative stress remains the key therapeutic target in neurological disease, it is necessary to explore the multiple routes that can significantly repair the damage caused due to ROS and consequently, neurodegenerative disorders (NDDs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the critical player of oxidative stress that can also be used as a therapeutic target to combat NDDs. Key findings Several antioxidants signalling pathways are found to be associated with oxidative stress and show a protective effect against stressors by increasing the release of various cytoprotective enzymes and also exert anti-inflammatory response against this oxidative damage. These pathways along with antioxidants and reactive species can be the defined targets to eliminate or reduce the harmful effects of neurological diseases. Summary Herein, we discussed the underlying mechanism and crucial role of antioxidants in therapeutics together with natural compounds as a pharmacological tool to combat the cellular deformities cascades caused due to oxidative stress

The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells

“…The increase in reactive oxygen species production and oxidative stress cause damage to cellular macromolecules such as DNA, lipids, and proteins, ultimately resulting in necrosis and apoptotic cell death and damage of proteasome and autophagy pathways, resulting in increased aggregation and toxicity of mutant htt ( Abramov et al, 2020 ). Therefore, inhibiting oxidative stress could represent an attractive therapeutic target to delay neurodegeneration in HD, although the origin of oxidative stress in the disease has been complicated ( Sharma et al, 2022 ). This study examined the potential neuroprotective effects of the well-known antioxidant luteolin and the mechanisms underlying the protection in the treated htt mutant cells.…”

Nanobubble technologies: Applications in therapy from molecular to cellular level

“…The increased level of oxygen in the affected area will assist the injured cells but the healthy tissue surrounding the affected site will also be subjected to the increased oxygen level. Oxidative stress has been linked to different neurological diseases (Sharma et al, 2022) and is also a factor in cancer growth due to oxidative DNA damage (Poulsen et al, 1998). The delivery of oxygen nanobubbles to patients with a predisposition to these diseases is therefore unwanted due to possible toxic side effects.…”

From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration

“…Various systems within the walls of blood arteries are responsible for generating ROS, including XO, eNOS, enzymes in the mitochondrial respiratory chain, and NADPH oxidase (NOXs) (Daiber et al, 2021;Burtscher et al, 2022;Leyane et al, 2022) These oxidases are complex enzymes composed of multiple subunits, which produce superoxide from molecular oxygen by utilizing NADPH as an electron supplier. They comprise two subunits associated with the membrane, along with several modulatory subunits located in the cytoplasm (Saxena and Jha, 2021;Sharma et al, 2022) Contrary to NOX1 and NOX2, NOX4 only requires p22phox (the ubiquitous protein encoded by the CYBA gene located on the long arm of chromosome 16 at position 24) and releases hydrogen peroxide instead of superoxide (Moghadam et al, 2021) Three NOX isotypes are expressed in the vascular smooth muscle cells (VSMC) that line the blood vessels of mice; two of these isotypes, NOX2 and NOX4, are preferentially expressed in endotheliocytes (Thiriet, 2015;Thiriet, 2018).…”