Article
Multidisciplinary Sciences
Andrija Sente, Rooma Desai, Katerina Naydenova, Tomas Malinauskas, Youssef Jounaidi, Jonas Miehling, Xiaojuan Zhou, Simonas Masiulis, Steven W. Hardwick, Dimitri Y. Chirgadze, Keith W. Miller, A. Radu Aricescu
Summary: In this study, the structures and arrangement diversity of GABA(A)Rs receptors were determined using cryogenic electron microscopy. It was found that different arrangements can affect receptor responses to modulators and that GABA(A)Rs receptors can simultaneously respond to two neurotransmitters. Through calculations and simulations, the researchers propose that differential assembly is a mechanism for regulating the function of GABA(A)Rs.
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Plant Sciences
Nova Syafni, Maria Teresa Faleschini, Aleksandra Garifulina, Ombeline Danton, Mahabir P. Gupta, Steffen Hering, Matthias Hamburger
Summary: Compounds isolated from Casearia corymbosa leaves showed allosteric potentiation of the GABA signal in GABAA receptors. The activity was confirmed through cell-based assays and voltage clamp studies.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Multidisciplinary Sciences
Chang Sun, Hongtao Zhu, Sarah Clark, Eric Gouaux
Summary: This study reveals the existence of different types of GABA receptors in the brain and the significant role of endogenous neurosteroids in modulating receptor function. These findings contribute to the development of subtype-specific drugs.
Article
Multidisciplinary Sciences
Khanh Vu Huu, Rene Zangl, Jan Hoffmann, Alicia Just, Nina Morgner
Summary: The study investigates the assembly process of F-1 complex from Acetobacterium woodii using laser induced liquid bead ion desorption mass spectrometry. The results indicate that nucleotide binding is crucial for in vitro assembly of F-1, while ATP hydrolysis is less critical. The study also proposes a model for the assembly pathway of a functional F-1 complex, correlating the results with activity measurements.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sijun Li, Xing Wei, Hongmi Huang, Lin Ye, Meigang Ma, Lanfeng Sun, Yuling Lu, Yuan Wu
Summary: This study found that NPTN may exert antiepileptic effects by binding to GABRA1 to inhibit the internalization of alpha 1-containing GABAaRs.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Frederik Rostrup, Christina B. Falk-Petersen, Kasper Harpsoe, Stine Buchleithner, Irene Conforti, Sascha Jung, David E. Gloriam, Tanja Schirmeister, Petrine Wellendorph, Bente Frolund
Summary: Research on DS2 analogues revealed that substituents at the 5-position of the imidazopyridine core scaffold greatly affect delta-selectivity and pharmacological profile. Among them, analogue 30 showed at least 60-fold selectivity for the α4β1δ receptor subtype, indicating a potential tool for selective characterization of delta-containing GABA(A)Rs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Craig A. Sexton, Reka Penzinger, Martin Mortensen, Damian P. Bright, Trevor G. Smart
Summary: This study reveals that spontaneous gating of GABA(A) receptors requires incorporation of beta 3 subunits, which is modulated by protein kinases and neurosteroids. This spontaneous activity alters neural network activity by regulating tonic inhibition.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Oleg Klykov, Shanti Pal Gangwar, Maria V. Yelshanskaya, Laura Yen, Alexander I. Sobolevsky
Summary: AMPARs mediate the majority of excitatory neurotransmission and their function is regulated by auxiliary subunits. Different types of TARP auxiliary subunits have different roles, and the structural and mechanistic variations of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.
Article
Neurosciences
Catherine Choi, Joshua L. Smalley, Abigail H. S. Lemons, Qiu Ren, Christopher E. Bope, Jake S. Dengler, Paul A. Davies, Stephen J. Moss
Summary: Impaired inhibitory signaling is the underlying cause of various neuropsychiatric and neurodevelopmental disorders. Synaptic and extrasynaptic GABA (A) Rs regulate neuronal inhibition through different subunit composition and interacting proteins. Differences in phosphorylation levels result in distinct assembly and expression patterns of GABA (A) Rs in different subtypes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Shaotong Zhu, Akshay Sridhar, Jinfeng Teng, Rebecca J. Howard, Erik Lindahl, Ryan E. Hibbs
Summary: GABA(A) receptors are important drug targets in the central nervous system for treating anxiety, sleep disorders, and epilepsy. This study presents two high-resolution structures of GABA(A) receptors bound by the drugs zolpidem and DMCM, providing insights into receptor modulation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Maria Julia Amundarain, Ernesto Raul Caffarena, Marcelo Daniel Costabel
Summary: The activation of GABA(A) receptors by the neurotransmitter gamma-aminobutyric acid mediates rapid inhibition response in the mammalian central nervous system. Alterations in these receptors can lead to various neurological and mental health disorders, with drugs like benzodiazepines targeting these receptors. It has been found that a specific amino acid in the alpha(1) subunit plays a role in drug binding, impacting the binding free energy and preferences for different ligands. Additionally, molecular dynamics simulations revealed water molecules that may play a role in the modulation mechanism of these receptors.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Pharmacology & Pharmacy
Xenia Simeone, Filip Koniuszewski, Markus Muellegger, Andreas Smetka, Friederike Steudle, Roshan Puthenkalam, Margot Ernst, Petra Scholze
Summary: The GABA(A) receptor family is an important drug target group for treating various disorders, and recent drug development research has focused on studying GABA(A) receptors containing the alpha 5 subunit.
MOLECULAR PHARMACOLOGY
(2021)
Article
Neurosciences
Shoko Nakamuta, Yoshio Yamamoto, Masao Miyazaki, Atsuhiro Sakuma, Masato Nikaido, Nobuaki Nakamuta
Summary: Lungfish have two distinct sensory epithelia in their olfactory organs, corresponding to the lamellar olfactory epithelium and primitive vomeronasal organ (VNO) found in teleosts and tetrapods, respectively. The expression of V1Rs, a type of olfactory receptor, in lungfish suggests an intermediate step in the segregation of V1R expression between the olfactory epithelium and VNO, reflecting the evolutionary position of lungfish between teleosts and amphibians.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Giovanna Carello-Collar, Bruna Bellaver, Pamela C. L. Ferreira, Joao Pedro Ferrari-Souza, Vanessa G. Ramos, Joseph Therriault, Cecile Tissot, Marco A. De Bastiani, Carolina Soares, Tharick A. Pascoal, Pedro Rosa-Neto, Diogo O. Souza, Eduardo R. Zimmer
Summary: This study conducted a systematic review with meta-analysis to investigate the role of the GABAergic system in Alzheimer's disease. The results showed a reduction in GABA levels in the brain and cerebrospinal fluid (CSF) of AD patients, suggesting the vulnerability of the GABAergic system in AD pathology.
MOLECULAR PSYCHIATRY
(2023)
Article
Medicine, Research & Experimental
Hui-Juan Wang, Ji-Hong Wang, Xin-Na Xu, Xing-Shan Zhao, Wei Liu
Summary: This study investigated the expression of ATP-binding cassette A1 and G1 in monocyte-derived macrophages in type 2 diabetes mellitus and their regulation by Liver X receptors. The results showed that the expression of ATP-binding cassette G1 and high density lipoprotein-induced cholesterol efflux were significantly reduced in type 2 diabetic patients. The study also suggested that impairment of cholesterol efflux and ATP-binding cassette G1 gene expression in type 2 diabetes mellitus might be regulated by a Liver X receptor-independent pathway.
CURRENT MOLECULAR MEDICINE
(2023)