Development of KCC2 therapeutics to treat neurological disorders [PDF]
Frontiers in Molecular NeuroscienceKCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS.
Shilpa D. Kadam, Shane V. Hegarty
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Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library [PDF]
Frontiers in Molecular NeuroscienceIntroductionThe neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission.
Pavel Uvarov +12 more
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Therapeutic potential for KCC2-targeted neurological diseases
Japanese Dental Science Review, 2023 Patients with neurological diseases, such as schizophrenia, tend to show low K+-Cl- co-transporter 2 (KCC2) levels in the brain. The cause of these diseases has been associated with stress and neuroinflammation.
Kazuo Tomita +11 more
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Effects of the ketogenic diet on dentate gyrus and CA3 KCC2 expression in male rats with electrical amygdala kindling-induced seizures [PDF]
Frontiers in NeuroscienceIntroductionKetogenic diet (KD), a high-fat, low-carbohydrate, and adequate protein diet, is a non-pharmacological treatment for refractory epilepsy. However, their mechanism of action is not fully understood.
Leticia Granados-Rojas +10 more
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Staurosporine and NEM mainly impair WNK-SPAK/OSR1 mediated phosphorylation of KCC2 and NKCC1.
PLoS ONE, 2020 The pivotal role of KCC2 and NKCC1 in development and maintenance of fast inhibitory neurotransmission and their implication in severe human diseases arouse interest in posttranscriptional regulatory mechanisms such as (de)phosphorylation. Staurosporine (
Jinwei Zhang +6 more
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Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions [PDF]
Frontiers in Molecular NeuroscienceDuring postnatal brain development, maintaining a delicate balance between excitation and inhibition (E/I) is essential for the precise formation of neuronal circuits.
Mohammad Naderi +3 more
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The Multifaceted Roles of KCC2 in Cortical Development [PDF]
Trends in Neurosciences, 2021 KCC2, best known as the neuron-specific chloride-extruder that sets the strength and polarity of GABAergic currents during neuronal maturation, is a multifunctional molecule that can regulate cytoskeletal dynamics via its C-terminal domain (CTD). We describe the molecular and cellular mechanisms involved in the multiple functions of KCC2 and its splice
Kai Kaila +6 more
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KCC2 is required for the survival of mature neurons but not for their development [PDF]
Journal of Biological Chemistry, 2021 The K+/Cl- cotransporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly ...
Shu Fun Josephine Ng +16 more
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The role of KCC2 in hyperexcitability of the neonatal brain [PDF]
Neuroscience Letters, 2020 The hyperpolarizing activity of γ-aminobutyric acid A (GABAA) receptors depends on the intracellular chloride gradient that is developmentally regulated by the activity of the chloride extruder potassium (K) chloride (Cl) cotransporter 2 (KCC2). In humans and rodents, KCC2 expression can be detected at birth.
Brock Matter +7 more
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Frontiers in Cell and Developmental Biology, 2022 KCC2 is a K+-Cl− cotransporter that is expressed in neurons throughout the central nervous system. Deficits in KCC2 activity have been implicated in a variety of neurological disorders, including epilepsy, chronic pain, autism spectrum disorders, and ...
Francis J. Prael III +12 more
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