Results 161 to 170 of about 5,952 (193)

Towards a KCC2 blocker pharmacophore model

Bioorganic & Medicinal Chemistry Letters, 2012
A multi-disciplinary approach was used to identify the first pharmacophore model for KCC2 blockers: several physico-chemical studies such as XRD and NMR were combined to molecular modelling techniques, SAR analysis and synthesis of constrained analogues in order to determine a minimal conformational space regrouping few potential bioactive ...
Lebon, Florence, Pégurier, Cécile, Ledecq, Marie, Mathieu, Benoit, Bosman, Nathalie, Frycia, Anne, Lengelé, Sébastien, Dhurke, Kashinath, Kanduluru, Ananda Kumar, Meunier, Stéphane, Wagner, Alain, Wolff, Christian, Provins, Laurent   +12 more
openaire   +2 more sources

KCC2, epileptiform synchronization, and epileptic disorders

Progress in Neurobiology, 2018
The K+-Cl- co-transporter KCC2 is a neuron-specific, Cl- extruder that uses K+ gradient for maintaining low intracellular [Cl-]. It is indeed well established that sustaining an outwardly-directed electrochemical Cl- gradient across the neuronal membrane is fundamental for a proper function of postsynaptic GABAA receptor signaling.
Graziella, Di Cristo, Patricia N, Awad, Shabnam, Hamidi, Massimo, Avoli   +3 more
openaire   +2 more sources

The KCC2 Cotransporter and Human Epilepsy

The Neuroscientist, 2016
The cation-Cl − cotransporter KCC2, encoded by SLC12A5, is required for the emergence and maintenance of GABAergic fast synaptic inhibition in organisms across evolution. These findings have suggested that KCC2 deficiency might play a role in the pathogenesis human epilepsy, but this has only
Kristopher T, Kahle, Arjun R, Khanna, JingJing, Duan, Kevin J, Staley, Eric, Delpire, Annapurna, Poduri   +5 more
openaire   +2 more sources

Behavioural phenotypes of hypomorphic KCC2‐deficient mice

European Journal of Neuroscience, 2005
AbstractHyperpolarizing fast inhibitory neurotransmission by γ‐aminobutyric acid and glycine requires an efficient chloride extrusion mechanism in postsynaptic neurons. A major effector of this task in adult animals is the potassium‐chloride co‐transporter KCC2 that is selectively and abundantly expressed postsynaptically in most CNS neurons.
Janne, Tornberg, Vootele, Voikar, Harri, Savilahti, Heikki, Rauvala, Matti S, Airaksinen   +4 more
openaire   +2 more sources

Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2

Journal of Molecular Neuroscience, 2022
Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders.
Giorgio Belperio, Claudia Corso, Carlos B. Duarte, Miranda Mele   +3 more
openaire   +2 more sources

Seizing Control of KCC2: A New Therapeutic Target for Epilepsy

Trends in Neurosciences, 2017
Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by ...
Nicholas J Brandon, Matt R Kelley, Tarek G Deeb   +2 more
exaly   +3 more sources

CIP1 is an activator of the K+–Cl− cotransporter KCC2

Biochemical and Biophysical Research Communications, 2009
In most neurons, efficient setting of the intracellular Cl(-)-concentration requires the coordinated regulation of the Cl(-)-inward transporter NKCC1 and the Cl(-)-outward transporter KCC2. Previously, the cation-chloride cotransporter interacting protein 1 (CIP1) was shown to inactivate NKCC1. Here, we investigated its role for KCC2 activity. After co-
Meike, Wenz, Anna-Maria, Hartmann, Eckhard, Friauf, Hans Gerd, Nothwang   +3 more
openaire   +2 more sources

Role of KCC2 in Auditory Processing of the Brainstem

2006
The present study indicates that the neuro-specific co-transporter KCC2 is expressed abundantly throughout the IC. The postnatal expression pattern of KCC2 is upregulated in the IC as well as that in the neocortex, the hippocampus and the cerebellum. Considering the importance of this co-transporter on controlling auditory function, further studies are
Motoi Kudo, Takaaki Nakamura, Kiyoshi Kurokawa   +2 more
openaire   +1 more source

Benzyl prolinate derivatives as novel selective KCC2 blockers

Bioorganic & Medicinal Chemistry Letters, 2010
The discovery and optimization of a novel class of selective submicromolar KCC2 blockers is described. Details of synthesis and SAR are given together with ADME properties of selected compounds. A methylsulfone residue on the R(1) phenyl group improved the overall general profile of these prolinate derivatives.
Cécile, Pégurier, Nathalie, Bosman, Philippe, Collart, Marie-Laure, Delporte, Karine, Leclercq, Sébastien, Lengelé, Ananda Kumar, Kanduluru, Stéphane, Meunier, Nathalie, Pacico, Lakshmana Rao, Vadali, Alain, Wagner, Christian, Wolff, Laurent, Provins   +12 more
openaire   +2 more sources

Genetic and environmental regulators of Kcc2/KCC2 gene expression

2020
Michele Yeo, Wolfgang Liedtke
openaire   +1 more source