Results 231 to 240 of about 121,181 (303)

Flecainide binding dynamics in voltage‐gated sodium channels: A comparative isoform analysis of the state‐dependent block

British Journal of Pharmacology, EarlyView.
Background and Purpose Local anaesthetics and class I anti‐arrhythmic drugs block voltage‐gated Na+ channels, but the molecular basis for the isoform differences in drug sensitivity remains unclear. Understanding these mechanisms is essential for optimizing therapeutic efficacy and safety.
Tatsuo Munakata, Etsuko Kumada, Nao Katayama, Hiroki Nakagawa, Akihiko Sunami   +4 more
wiley   +1 more source

Cannabinoid and adenosine A2A receptor crosstalk regulates postnatal and adult hippocampal neurogenesis

British Journal of Pharmacology, EarlyView.
Background and purpose Adult neurogenesis is a tightly regulated process affected by both cannabinoid receptors (CB1 and CB2) and adenosine 2A (A2A) receptors, both of which modulate neural progenitor cell activity. While emerging evidence suggests an interaction between these neuromodulatory systems, the extent and mechanism of their interplay in ...
Rui S. Rodrigues, Adam Armada‐Moreira, Laura Gómez‐Acero, Filipa F. Ribeiro, Francisco M. Mouro, Ana M. Sebastião, Francisco Ciruela, Ester Aso, Sara Xapelli   +8 more
wiley   +1 more source

Prevention of microglial activation and postoperative cognitive deficits by positive allosteric modulation of α5‐GABAA receptors

British Journal of Pharmacology, EarlyView.
Background and Purpose Long‐lasting cognitive deficits after surgery in aged individuals, referred to as perioperative neurocognitive disorder (NCD), are a significant public health concern. Such postoperative cognitive deficits are dependent on the presence of microglia in the brain, which, when activated, trigger neuroinflammation.
Jinrui Lyu, Rajasekar Nagarajan, Dishary Sharmin, Prithu Mondal, Maltesh Kambali, Muxiao Wang, Jinyan Zhou, Makoto Inoue, James M. Cook, Uwe Rudolph   +9 more
wiley   +1 more source

Agonist‐specific conformational dynamics at the β2‐adrenoceptor dictate allosteric modulation of Gαs signalling and bronchodilation

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose β2‐adrenoceptor (β2AR) agonists are the cornerstone of asthma therapy and promote bronchodilation through Gαs signalling in airway smooth muscle (ASM), but their efficacy is limited by β‐arrestin‐mediated β2AR desensitization.
Sushrut D. Shah, Joshua Richard, Suvankar Ghosh, Jillian Jerwick, Joice T. Gavali, Raymond B. Penn, Alexander D. MacKerell Jr, Deepak A. Deshpande   +7 more
wiley   +1 more source

Inhibition of kynurenine 3‐monooxygenase (KMO) reduces fentanyl and sucrose intake and relapse‐like behaviour in rats

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Opioid use disorder, particularly involving fentanyl, poses major challenges due to high relapse rates and limited effectiveness of pharmacotherapies. The kynurenine pathway has emerged as a target for addiction treatment through its modulation of glutamatergic and dopaminergic neurotransmission.
Carlos Núñez‐de la Calle, Lluna Careaga, Stefanie Malan‐Müller, Álvaro del Río‐García, Yaiza Trueba, Leticia Gil de Biedma‐Elduayen, Nuria Morales‐Puerto, Rebeca Vidal, Åsa Wiman, Sophie Erhardt, María Dolores Gutiérrez‐López, Esther O'Shea, María Isabel Colado   +12 more
wiley   +1 more source

Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior

The FEBS Journal, EarlyView.
Irreversible ECM proteolysis by remodeling enzymes shapes development, homeostasis, and disease. ECM‐degrading proteases display cell specificity and are governed by shared mechanisms, exhibiting functional redundancy in generating matrikines, growth factors, and cytokines.
Inna Solomonov, Orit Kollet, Irit Sagi
wiley   +1 more source

Species-Specific Involvement of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of the Pyrimidine-Containing mGlu5-Negative Allosteric Modulator VU0424238 (Auglurant)

Drug Metabolism And Disposition, 2017
R. Crouch, A. L. Blobaum, Andrew S. Felts, P. J. Conn, C. Lindsley   +4 more
semanticscholar   +1 more source

Quantitative analysis of DNA‐GATA1 binding alterations linked to hematopoietic disorders

The FEBS Journal, EarlyView.
Native holdup allows the quantitative determination of affinities between full‐length transcription factors and DNA. Mutations in either the protein or the DNA can modulate binding strength, which can be precisely quantified using this approach. Applied to GATA1, it revealed mutations that alter DNA binding.
Boglarka Zambo, Bastien Morlet, Luc Negroni, Orsolya Mózner, Balázs Sarkadi, Gilles Travé, Gergo Gogl   +6 more
wiley   +1 more source

Investigating transthyretin variants H88R and I107V in amyloid priming: From destabilization to complete dissociation

The FEBS Journal, EarlyView.
Investigated mutations in transthyretin (TTR) disrupt the F87‐centered hydrophobic core that stabilizes its tetrameric structure. The mild I107V mutation weakens inter‐chain packing, while H88R fully abolishes tetramer formation, yielding a monomeric, aggregation‐prone form. Structural, biophysical, and computational analyses reveal that both mutations
István L. Bódy, Zsolt Fazekas, Nóra Wágner, Anna J. Kiss‐Szemán, Veronika Harmat, Zoltán Pozsonyi, Dóra K. Menyhárd, András Perczel   +7 more
wiley   +1 more source

Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease

The FEBS Journal, EarlyView.
The extracellular matrix (ECM) is a dynamic scaffold that orchestrates tissue architecture and cellular communication. A critical but underexplored interplay between proteases and cluster of differentiation molecules (CD) governs ECM turnover and directs cell fate.
David Jurnečka, Matija Hrovatin, Bor Bokalj, Boris Turk   +3 more
wiley   +1 more source