Miniatura

Fitxers

833218.pdf (4.28 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2023-10-11

Llicència de publicació

cc by-nc-nd (c) Mona Peyman, et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/217146

Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1016/j.biopha.2023.115667

Resum

Soluble epoxide hydrolase (sEH) is a drug target with the potential for therapeutic utility in the areas of inflammation, neurodegenerative disease, chronic pain, and diabetes, among others. Proteolysis-targeting chimeras (PROTACs) molecules offer new opportunities for targeting sEH, due to its capacity to induce its degradation. Here, we describe that the new ALT-PG2, a PROTAC that degrades sEH protein in the human hepatic Huh-7 cell line, in isolated mouse primary hepatocytes, and in the liver of mice. Remarkably, sEH degradation caused by ALT-PG2 was accompanied by an increase in the phosphorylated levels of AMP-activated protein kinase (AMPK), while phosphorylated extracellular-signal-regulated kinase 1/2 (ERK1/2) was reduced. Consistent with the key role of these kinases on endoplasmic reticulum (ER) stress, ALT-PG2 attenuated the levels of ER stress and inflammatory markers. Overall, the findings of this study indicate that targeting sEH with degraders is a promising pharmacological strategy to promote AMPK activation and to reduce ER stress and inflammation.

Matèries

Epòxids, Inflamació, Neurologia

Matèries (anglès)

Epoxy compounds, Inflammation, Neurology

Citació

Col·leccions

Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

PEYMAN, Mona, BARROSO FERNÁNDEZ, Emma, TURCU, Andreea l., ESTRANY JR, Francesc, SMITH, Dáire, JURADO AGUILAR, Javier, RADA, Patricia, MORISSEAU, Christophe, HAMMOCK, Bruce d., VALVERDE, Ángela m., PALOMER TARRIDAS, Francesc xavier, GALDEANO CANTADOR, Carlos, VÁZQUEZ CRUZ, Santiago, VÁZQUEZ CARRERA, Manuel. Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress. _Biomedicine & Pharmacotherapy_. 2023. Vol. 168, núm. 115667. [consulta: 21 de gener de 2026]. ISSN: 0753-3322. [Disponible a: https://hdl.handle.net/2445/217146]

Exportar metadades

JSON - METS

Compartir registre