Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 20, 2024

Uncontrolled and chronic inflammatory states in the Central Nervous System (CNS) are hallmark of neurodegenerative pathology every injury or stroke-related insult. The key mediators these neuroinflammatory glial cells known as microglia, resident immune cell at core event, astroglia, which encapsulate insults proteoglycan-rich scar tissue. Since majority neuroinflammation is exclusively based on responses said glia, their phenotypes have been identified to be an spectrum encompassing developmental, homeostatic, reparative behaviors opposed ability affect devastating death cascades tissue formation. Recently, research groups focused peptide discovery identify phenotypes, find novel mechanisms, mediate re-engineer actions. Peptides retain diverse function proteins but significantly reduce activity dependence delicate 3D structures. Several peptides targeting unique microglia astroglia identified, along with several capable mediating deleterious promoting beneficial outcomes context neuroinflammation. A comprehensive review will provided primary methodologies, including top-down approaches using biomolecules naïve strategies phage libraries.

Language: Английский

Chiisanoside from the Leaves of Acanthopanax sessiliflorus Can Resist Cisplatin-Induced Ototoxicity by Maintaining Cytoskeletal Homeostasis and Inhibiting Ferroptosis

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(46), P. 25720 - 25742

Published: Nov. 6, 2024

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology screening determined that chiisanoside (CSS) plays crucial role combating Transcriptomics combined with network experiments revealed CSS activates Dock1/PIP5K1A pathway suppress actin-severing protein gelsolin, protecting hair cells from cytoskeleton damage. also SLC7A11/GPX4 via TGFBR2, reducing lipid peroxidation intracellular iron accumulation ferroptosis. discovers major component A. reverses CIO by regulating actin homeostasis Dock1 inhibiting ferroptosis through providing theoretical basis for expanding treatment targets related drug development.

Language: Английский