Results 111 to 120 of about 107,657 (326)

Functional Analysis of Ligand‐Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling

Advanced Science, EarlyView.
We uncover a large variety of putative inhibitory ligand‐gated ion channels (LGICs) in the phylum Cnidaria, the sister group to all bilaterian animals. Phylogenetic analysis suggests a complex evolutionary history of inhibitory LGICs with diverse neurotransmitter ligands.
Abhilasha Ojha, Linda Kloss, Juan D. Montenegro, Simone Albani, Audrey Ortega‐Ramírez, Mihaela Raycheva, Sylvia Joussen, Sabrina Kaul, Michèle Bachmann, Lisa Huf, Günther Schmalzing, Alison G. Cole, Ulrich Technau, Stefan Gründer   +13 more
wiley   +1 more source

Antinociceptive effects of a novel α2/α3 subtype selective GABAA receptor positive allosteric modulator

ACS Chemical Neuroscience, 2017
Pain remains a challenging clinical condition and spinal GABAA receptors are crucial modulators of pain processing. α2/α3-subtype GABAA receptors mediate the analgesic actions of benzodiazepines.
Lakeisha A. Lewter, J. Fisher, Justin N Siemian, K. R. Methuku, M. Poe, J. Cook, Jun-Xu Li   +6 more
semanticscholar   +1 more source

PRMT1‐Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis

Advanced Science, EarlyView.
This study identifies an immunometabolic axis wherein SAM‐driven PRMT1 methylates LDHA, enhancing its activity. The resultant lactate induces STAT3 K709 lactylation, which stabilizes an active conformation to promote STAT3 phosphorylation and IL‐10 expression.
Hui Wang, Mengyu Zhang, Weipeng Gong, Jiaxuan Wu, Junping Zhang, Wenxiu Zhang, Yue Liu, Kui Wang, Canhua Huang, Jun Zhou, Sijin Wu, Yan Li, Tianliang Li   +12 more
wiley   +1 more source

Pronounced antiepileptic activity of the subtype‐selective GABAA‐positive allosteric modulator PF‐06372865 in the GAERS absence epilepsy model

CNS Neuroscience & Therapeutics, 2018
Antiepileptic drugs that modulate GABA have the potential to aggravate or improve the symptoms of absence epilepsy. PF‐06372865 is a positive allosteric modulator (PAM) of α2/3/5 subunit‐containing GABAA receptors with minimal activity at α1‐containing ...
V. Duveau, D. Buhl, A. Evrard, C. Ruggiero, Betty Mandé-Niedergang, C. Roucard, R. Gurrell   +6 more
semanticscholar   +1 more source

Positive Allosteric Modulation of SK Channels by Riluzole

Biophysical Journal, 2016
Small conductance Ca2+-activated potassium (SK) channels play a key role in the regulation of neuronal excitability. Positive modulation of potassium ion channels has been suggested as a potential therapeutic strategy to normalize the excitability of neurons, in movement disorders such as ataxia and Amyotrophic Lateral Sclerosis (ALS).
Nam, Young-Woo, Ali, Sara, Chiang, Stephen, Alexander, Tia, Zhang, Miao   +4 more
openaire   +1 more source

MK-7622: A First-in-Class M₁ Positive Allosteric Modulator Development Candidate

, 2018
Identification of ligands that selectively activate the M1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders.
Kenneth A. Koeplinger (1811914), Charles D. Thompson (1811923), Christina N. Di Marco (2268625), Scott D. Kuduk (1811911), Matthew A. Seager (1811908), Joy Fuerst (5175641), George D. Hartman (2183106), Lei Ma (221178), William J. Ray (190662), Ronald K. Chang (2013505), Thomas J. Greshock (2178438), Marion Wittmann (1811926), Mark T. Bilodeau (1779970), Douglas C. Beshore (2414380)   +13 more
core   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

Advanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng, Yanlin Guo, Liumi Jiang, Jing Luo, Yan Liu, Ziwei Yuan, Pingyang Ke, Ran Duan, Fei Xiao   +8 more
wiley   +1 more source

Autoimmune Encephalitis in Acute Care—Pathology, Diagnosis, and Management

Advanced Science, EarlyView.
ABSTRACT Autoimmune encephalitis (AE) is characterized by immune‐mediated inflammation of the brain parenchyma, presenting with various neurological syndromes, including but not limited to seizures, altered consciousness, neuropsychiatric symptoms, and movement disorders.
Suneesh Thilak, David Okoh, William Scotton, Shanika Samarasekera, Vikram Patil, Suresh Renukappa, Andrew Macduff, Subashini Suresh, Rajeev Krishnadas, Tonny Veenith   +9 more
wiley   +1 more source

PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems

ACS Chemical Neuroscience, 2018
Positive allosteric modulators (PAMs) of the M1 subtype of muscarinic acetylcholine receptor have attracted intense interest as an exciting new approach for improving the cognitive deficits in schizophrenia and Alzheimer’s disease.
Sean P. Moran, Hyekyung P. Cho, James Maksymetz, Daniel H. Remke, Ryan M Hanson, C. Niswender, C. Niswender, C. Lindsley, J. M. Rook, P. Conn   +9 more
semanticscholar   +1 more source

Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects.

, 2015
Activation of nicotinic acetylcholine receptors (nAChRs) is associated with the binding of agonists such as acetylcholine to an extracellular site that is located at the interface between two adjacent receptor subunits.
Dhankher, P, Gill-Thind, JK, D'Oyley, JM, Sheppard, TD, Millar, NS   +4 more
core