The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington’s Disease and Its Comorbidities
dc.contributor.author | Anfrews, K | |
dc.contributor.author | Josiah, SS | |
dc.contributor.author | Zhang, J | |
dc.date.accessioned | 2020-12-01T09:02:31Z | |
dc.date.issued | 2020-11-30 | |
dc.description.abstract | Intracellular chloride levels in the brain are regulated primarily through the opposing effects of two cation-chloride co-transporters (CCCs), namely K+-Cl− co-transporter-2 (KCC2) and Na+-K+-Cl− co-transporter-1 (NKCC1). These CCCs are differentially expressed throughout the course of development, thereby determining the excitatory-to-inhibitory γ-aminobutyric acid (GABA) switch. GABAergic excitation (depolarisation) is important in controlling the healthy development of the nervous system; as the brain matures, GABAergic inhibition (hyperpolarisation) prevails. This developmental switch in excitability is important, as uncontrolled regulation of neuronal excitability can have implications for health. Huntington’s disease (HD) is an example of a genetic disorder whereby the expression levels of KCC2 are abnormal due to mutant protein interactions. Although HD is primarily considered a motor disease, many other clinical manifestations exist; these often present in advance of any movement abnormalities. Cognitive change, in addition to sleep disorders, is prevalent in the HD population; the effect of uncontrolled KCC2 function on cognition and sleep has also been explored. Several mechanisms by which KCC2 expression is reduced have been proposed recently, thereby suggesting extensive investigation of KCC2 as a possible therapeutic target for the development of pharmacological compounds that can effectively treat HD co-morbidities. Hence, this review summarizes the role of KCC2 in the healthy and HD brain, and highlights recent advances that attest to KCC2 as a strong research and therapeutic target candidate. | en_GB |
dc.description.sponsorship | Commonwealth PhD Scholarship | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.identifier.citation | Vol. 21 (23), article 9142 | en_GB |
dc.identifier.doi | 10.3390/ijms21239142 | |
dc.identifier.grantnumber | R01 NS109358 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/123847 | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.rights | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.subject | GABAergic | en_GB |
dc.subject | Na+-K+-2Cl− cotransporter 1 (NKCC1) | en_GB |
dc.subject | K+-2Cl− cotransporter 2 (KCC2) | en_GB |
dc.subject | Chloride (Cl−) homeostasis | en_GB |
dc.subject | Huntington’s disease | en_GB |
dc.subject | sleep disorders | en_GB |
dc.title | The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington’s Disease and Its Comorbidities | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-12-01T09:02:31Z | |
dc.description | This is the final version. Available on open access from MDPI via the DOI in this record | en_GB |
dc.identifier.eissn | 1422-0067 | |
dc.identifier.journal | International Journal of Molecular Sciences | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-11-28 | |
exeter.funder | ::National Institutes of Health | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-11-30 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-12-01T09:00:10Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-12-01T09:02:48Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).