Results 91 to 100 of about 19,325 (262)

Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target

Annals of Neurology, EarlyView.
Objective Biallelic variants in PRKN cause autosomal recessive Parkinson's disease (PD) with a median age at onset of 31 years. When evaluating the 16 previously published carriers of a homozygous deletion of Exon 2 from the International Parkinson's Disease and Movement Disorder Society Gene Database (MDSGene) database, the median age at onset is ...
Arian Hach, Katja Lohmann, Manabu Funayama, Poornima J. Menon, Eva‐Juliane Vollstedt, Teresa Kleinz, Hiroyo Yoshino, Suzanne Lesage, Britta Meier, Carolyn M. Sue, Jean‐Christophe Corvol, Alexis Brice, Nobutaka Hattori, Christine Klein, Aleksandar Rakovic   +14 more
wiley   +1 more source

Structural Mechanism of an Efficacy Photoswitch Targeting the β2‐adrenergic Receptor

Angewandte Chemie International Edition, EarlyView.
Time‐resolved structures from x‐ray free‐electron laser measurements combined with cellular assays demonstrate how the photoswitchable β‐blocker photoazolol‐1 acts as an efficacy switch of β2‐adrenergic receptor function. Light‐induced ligand repositioning shifts activity from inverse agonism toward neutral antagonism by altering local helical ...
Robin Stipp, Quentin Bertrand, Matilde Trabuco, Anna Duran‐Corbera, Maria Tindara Ignazzitto, Hannah Glover, Fabienne Stierli, Juanlo Catena, Melissa Carrillo, Sina Hartmann, Hans‐Peter Seidel, Matthias Mulder, Thomas Mason, Yasushi Kondo, Maximillian Wranik, Martin Appleby, Christoph Sager, Raymond Sierra, Gregory Gate, Pamela Schleissner, Xinxin Cheng, Tobias Weinert, Robert Cheng, Sandra Mous, John H. Beale, Michal Kepa, Amadeu Llebaria, Michael Hennig, Xavier Rovira, Joerg Standfuss   +29 more
wiley   +1 more source

Protein‐Driven Copper Redox Regulation: Uncovering the Role of Disulphide Bonds and Allosteric Modulation

Angewandte Chemie International Edition, EarlyView.
Copper binding triggers structural changes that expose a reactive disulphide bridge, enabling intrinsic Cu(II) reduction in folded proteins. SAXS, XAS, and QM/MM simulations reveal how globular proteins such as HSA and SOD1 employ disulphide‐mediated dynamics to modulate site accessibility and control copper redox chemistry.
Rebecca Sternke‐Hoffmann, Chang Liu, Xue Wang, Hegne Pupart, Xun Sun, Jan Gui‐Hyon Dreiser, Peep Palumaa, Qinghua Liao, Matthias Krack, Jinghui Luo   +9 more
wiley   +1 more source

Lipid Pocket Binders Impose Allosteric Changes of Protein Dynamics Around the Active Site of the Protein Kinase p38α

Angewandte Chemie International Edition, EarlyView.
Used in search of novel allosteric sites in the serine/threonine kinase p38α, NMR spectroscopy reveals a dynamic coupling between the catalytic and lipid pockets. The findings uncover a motional interdependence that links distant regions of the enzyme, highlighting the lipid pocket as a promising site for allosteric intervention.
Sara Medina Gómez, Laurin T. Homberg, Mike Bührmann, Daniel Rauh, Rasmus Linser   +4 more
wiley   +1 more source

Controlled Delivery and Light‐Induced Release of Magic Spot Nucleotides in Escherichia coli

Angewandte Chemie International Edition, EarlyView.
We synthesized photocaged, clickable and isotope‐labeled “magic spot” Nucleotides and delivered them into Escherichia coli comparing different approaches. Light‐controlled release inside living cells enabled tracking of their conversion from pppGpp to ppGpp by capillary electrophoresis mass spectrometry and revealed their impact on the growth rate of a
Christoph Popp, Patrick Moser, Anselm Schwoerbel, Xinwei Liu, Johannes Freitag, Pinku Sarmah, Isabel Prucker, Robert Zscherp, Xuan Wang, Philipp Klahn, Hans‐Georg Koch, Gert Bange, Henning J. Jessen   +12 more
wiley   +1 more source

Inosine triphosphate pyrophosphatase activity as a potential predictor of methotrexate remission in juvenile idiopathic arthritis

Arthritis &Rheumatology, Accepted Article.
Background Methotrexate (MTX) is the first‐line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients don't respond. Low inosine‐triphosphate‐pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated ITPA role and the underlying mechanisms in vitro.
Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L. Becker, Laura B. Ramsey, Susan D. Thompson, Carl D. Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore   +19 more
wiley   +1 more source

Cannabinoids and drug–drug pharmacokinetic interactions: Deciphering the risks

British Journal of Clinical Pharmacology, EarlyView.
The relationship between cannabinoids and mental health has become a major focus of scientific inquiry and public discourse. Cannabinoids are diverse chemical compounds from the Cannabis species that have been explored for their therapeutic applications in treating chronic pain, psychiatric and neurological conditions, such as depression, schizophrenia,
Paraskevi Papakyriakopoulou, Georgia Valsami, Georgios Ismailos   +2 more
wiley   +1 more source

Zuranolone: A case study in (regulatory) rush to judgement?

British Journal of Clinical Pharmacology, EarlyView.
Abstract Sage, in collaboration with Biogen, submitted a new drug approval for zuranolone for postpartum depression (PPD) and major depressive disorder (MDD) in December 2022. In August 2023, the US Food and Drug Administration granted approval for PPD but denied approval for MDD.
Lisa Cosgrove, Milutin Kostic, Barbara Mintzes, Gianna D'Ambrozio, Allen Shaughnessy   +4 more
wiley   +1 more source

The free fatty acid 2 receptor regulates C5a induced neutrophil superoxide production and its sensitivity to inhibition by the antagonist avacopan

Frontiers in Immunology
IntroductionReceptor transactivation is a novel signaling mechanism used by several different neutrophil G protein-coupled receptors (GPCRs) to activate an allosterically modulated receptor that recognizes short chain free fatty acids.
Zahra Khan, Zahra Khan, Neele K. Levin, Claes Dahlgren, Martina Sundqvist, Fariha Khan, Huamei Forsman, Huamei Forsman, Lena Björkman   +8 more
doaj   +1 more source

GLP‐1 agonists and the gut microbiome: A bidirectional relationship

British Journal of Clinical Pharmacology, EarlyView.
Abstract Glucagon‐like peptide‐1 (GLP‐1) receptor agonists have transformed the management of type 2 diabetes mellitus (T2DM) and obesity, yet their interactions with the gut microbiome remain an emerging frontier in pharmacological and metabolic research.
Srinivas Kamath, Nicole S. L. Chan, Paul Joyce   +2 more
wiley   +1 more source