To activate a G protein-coupled receptor permanently with cell surface photodynamic action in the gastrointestinal tract

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(12)

Published: March 26, 2025

Different from reversible agonist-stimulated receptor activation, singlet oxygen oxidation activates permanently G protein-coupled (GPCR) cholecystokinin 1 (CCK1R) in type II photodynamic action, with soluble photosensitizer dyes (sulphonated aluminum phthalocyanine, λmax 675 nm) or genetically encoded protein photosensitizers (KillerRed 585 nm; mini generator 450 nm), together a pulse of light (37 mW/cm2, 1-2 minutes). Three lines evidence shed on the mechanism GPCR activated by (GPCR-ABSO): (1) CCK1R is quantitatively converted dimer to monomer; (2) Transmembrane domain 3, pharmacophore for permanent can be transplanted non-susceptible M3 acetylcholine receptor; and (3) Larger size disordered region intracellular loop 3 correlates higher sensitivity activation. GPCR-ABSO will add arsenal engineered designer such as receptors solely synthetic ligands exclusively drugs, but show some clear advantages: Enhanced selectivity (double localized illumination), long-lasting activation no need repeated drug administration, antagonist-binding site remains intact when needed, ease apply multiple GPCR. This may applied functional proteins other than

Language: Английский

Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer’s Disease: Isoform-Specific Contributions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12299 - 12299

Published: Nov. 15, 2024

Oxidative stress is linked to the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder marked by memory impairment and cognitive decline. AD characterized accumulation amyloid-beta (Aβ) plaques formation neurofibrillary tangles (NFTs) hyperphosphorylated tau. associated with an imbalance in redox states excessive reactive oxygen species (ROS). Recent studies report that NADPH oxidase (NOX) enzymes are significant contributors ROS generation diseases, including AD. NOX-derived aggravates oxidative neuroinflammation during In this review, we provide potential role all NOX isoforms their respective structural involvement progression, highlighting as strategic therapeutic target. A comprehensive understanding inhibitors could valuable insights into pathology aid development targeted treatments for

Language: Английский

Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy—A State-of-the-Art Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1578 - 1578

Published: Dec. 21, 2024

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential serious adverse effects. Ototoxicity from cisplatin important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval sodium thiosulphate prevention cisplatin-induced loss (CIHL) in pediatric patients, structured programs are not routinely implemented most hospitals, reducing platinum-induced ototoxicity adults remains clinical problem without options. Cochlear oxidative stress plays fundamental role CIHL. Here, we review molecular mechanisms leading to CIHL preclinical studies testing antioxidants guide future trials assessing efficacy safety candidate antioxidant compounds this setting.

Language: Английский