Results 61 to 70 of about 31,985 (308)

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models. [PDF]

, 2020
NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via
Chan, Connie, Chen, Yelin, Deshmukh, Gauri, Elstrott, Justin, Gill, T Michael, Hackos, David H, Hanson, Jesse E, Jiang, Zhiyu, Khan, Abdullah S, Kim, Thomas A, Liederer, Bianca M, Liu, Benjamin, Ma, Keran, Palop, Jorge J, Saillet, Sandrine, Scearce-Levie, Kimberly, Schwarz, Jacob B, Sellers, Benjamin D, Sheng, Morgan, Simms, Jeffrey, Solanoy, Hilda, Volgraf, Matthew, Wang, Tzu-Ming, Weber, Martin, Weimer, Robby M, Yu, Gui-Qiu   +25 more
core   +1 more source

M1 receptor positive allosteric modulators discovery approaches

Trends in Pharmacological Sciences
The development of M1 muscarinic acetylcholine-receptor-positive allosteric modulators has been hindered by their limited cognitive efficacy and cholinergic side effects. We discuss two unique approaches - low intrinsic agonism and low binding cooperativity - that were developed to address these issues and their therapeutic implications.
Takao Mandai, Arthur A. Simen, Antonio Laurenza, Haruhide Kimura   +3 more
openaire   +2 more sources

Positive allosteric modulation of the adenosine A2a receptor attenuates inflammation [PDF]

Journal of Inflammation, 2014
Adenosine is produced at high levels at inflamed sites as a by-product of cellular activation and breakdown. Adenosine mediates its anti-inflammatory activity primarily through the adenosine A2a receptor (A2aR), a member of the G-protein coupled receptors. A2aR agonists have demonstrated anti-inflammatory efficacy, however, their therapeutic utility is
Welihinda, Ajith A, Amento, Edward P
openaire   +2 more sources

Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107

Journal of Neuroinflammation, 2021
Background The α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells.
Tehila Mizrachi, Oshrit Marsha, Karen Brusin, Yael Ben-David, Ganesh A. Thakur, Adi Vaknin-Dembinsky, Millet Treinin, Talma Brenner   +7 more
doaj   +1 more source

A clickable oxysterol photolabel retains NMDA receptor activity and accumulates in neurons [PDF]

, 2018
Oxysterol analogs that modulate NMDA receptor function are candidates for therapeutic development to treat neuropsychiatric disorders. However, the cellular actions of these compounds are still unclear.
Benz, Ann, Chen, Daniel M, Covey, Douglas F, Mennerick, Steven, Qian, Mingxing, Ziolkowski, Luke, Zorumski, Charles F   +6 more
core   +3 more sources

Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor [PDF]

, 2014
Background: Selective and potent positive allosteric modulators (PAMs) of the M1 mAChR have been recently described. Results: Use of structural analogues and mutagenic mapping identified the mechanistic basis for increased PAM activity.
Abdul-Ridha, Byun, Canals, Christopoulos, Conn, Conn, Dror, Foster, Haga, Hulme, Jones, Katritch, Kenakin, Kennedy, Keov, Kruse, Kruse, Kruse, Kuduk, Kuduk, Kuduk, Lazareno, Leach, Leach, Lebois, Lebon, Ma, Matsui, May, Melancon, Mistry, Motulsky, Nathan, Nawaratne, Nickols, Phillips, Ragnarsson, Shirey, Shonberg, Stevens, Tarr, Valant, Venkatakrishnan   +42 more
core   +2 more sources

Molecular bases of circadian magnesium rhythms across eukaryotes

FEBS Letters, EarlyView.
Circadian rhythms in intracellular [Mg2+] exist across eukaryotic kingdoms. Central roles for Mg2+ in metabolism suggest that Mg2+ rhythms could regulate daily cellular energy and metabolism. In this Perspective paper, we propose that ancestral prokaryotic transport proteins could be responsible for mediating Mg2+ rhythms and posit a feedback model ...
Helen K. Feord, Gerben van Ooijen
wiley   +1 more source

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

, 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.
D'Oyley, JM, Dhankher, P, Gill-Thind, JK, Millar, NS, Sheppard, TD   +4 more
core  

Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets

FEBS Letters, EarlyView.
Cryptochrome and PAS/LOV proteins play intricate roles in circadian clocks where they act as both sensors and mediators of protein–protein interactions. Their ubiquitous presence in signaling networks has positioned them as targets for small‐molecule therapeutics. This review provides a structural introduction to these protein families.
Eric D. Brinckman, Anna E. Lester, Brian D. Zoltowski   +2 more
wiley   +1 more source

Molecular and cellular factors control signal transduction via switchable allosteric modulator proteins (SAMPs) [PDF]

, 2016
Background: Rap proteins from Bacilli directly target response regulators of bacterial two-component systems and modulate their activity. Their effects are controlled by binding of signaling peptides to an allosteric site. Hence Raps exemplify a class of
Babel, Heiko, Bischofs, Ilka B.
core   +1 more source