RT Journal Article
T1 Drug screening targeting TREM2-TYROBP transmembrane binding.
A1 Cobas-Carreño, María
A1 Esteban-Martos, Alvaro
A1 Tomas-Gallardo, L
A1 Iribarren, I
A1 Gonzalez-Palma, L
A1 Rivera-Ramos, A
A1 Elena-Guerra, J
A1 Alarcón-Martín, Emilio
A1 Ruiz, R
A1 Bravo, MJ
A1 Venero, José Luis
A1 Morató, X
A1 Ruíz, Agustín
A1 Royo-Sánchez-Palencia, José Luis
K1 Alzheimer, Enfermedad de - Investigación
K1 Medicamentos - Ensayos
AB TREM2 encodes a microglial membrane receptor involved in the disease-associated microglia (DAM) phenotype whose activation requires the transmembrane interaction with TYROBP. Mutations in TREM2 represent a high-impact risk factor for Alzheimer's disease (AD) which turned TREM2 into a significant drug target. We present a bacterial two-hybrid (B2H) system designed for high-throughput screening of modulators for the TREM2-TYROBP transmembrane interaction. In a pilot study, 315 FDA-approved drugs were analyzed to identify potential binding modifiers. Our pipeline includes multiple filtering steps to ensure candidate specificity. The screening suggested two potential candidates that were finally assayed in the human microglial cell line HMC3. Upon stimulation with anti-TREM2 mAb, pSYK/SYK ratios were calculated in the presence of the candidates. As a result, we found that varenicline, a smoking cessation medication, can be considered as a transmembrane agonist of the TREM2-TYROBP interaction.
PB Spinger Nature
YR 2025
FD 2025
LK https://hdl.handle.net/10630/38552
UL https://hdl.handle.net/10630/38552
LA eng
NO Cobas-Carreño, M., Esteban-Martos, A., Tomas-Gallardo, L. et al. Drug screening targeting TREM2-TYROBP transmembrane binding. Mol Med 31, 171 (2025). https://doi.org/10.1186/s10020-025-01229-y
NO Fundacion ACE
NO Fundacion SantÁngela
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026