{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:07:03Z","timestamp":1790716023051,"version":"4.1.0"},"reference-count":131,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T00:00:00Z","timestamp":1579219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dysfunctions in GABAergic inhibitory neural transmission occur in neuronal injuries and neurological disorders. The potassium\u2013chloride cotransporter 2 (KCC2, SLC12A5) is a key modulator of inhibitory GABAergic inputs in healthy adult neurons, as its chloride (Cl\u2212) extruding activity underlies the hyperpolarizing reversal potential for GABAA receptor Cl\u2212 currents (EGABA). Manipulation of KCC2 levels or activity improve symptoms associated with epilepsy and neuropathy. Recent works have now indicated that pharmacological enhancement of KCC2 function could reactivate dormant relay circuits in an injured mouse\u2019s spinal cord, leading to functional recovery and the attenuation of neuronal abnormality and disease phenotype associated with a mouse model of Rett syndrome (RTT). KCC2 interacts with Huntingtin and is downregulated in Huntington\u2019s disease (HD), which contributed to GABAergic excitation and memory deficits in the R6\/2 mouse HD model. Here, these recent advances are highlighted, which attest to KCC2\u2019s growing potential as a therapeutic target for neuropathological conditions resulting from dysfunctional inhibitory input.<\/jats:p>","DOI":"10.3390\/cells9010240","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The Expanding Therapeutic Potential of Neuronal KCC2"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-636X","authenticated-orcid":false,"given":"Bor Luen","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"},{"name":"NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112224","DOI":"10.1016\/j.bbr.2019.112224","article-title":"\u0393-Aminobutyric acid in adult brain: an update","volume":"376","author":"Siucinska","year":"2019","journal-title":"Behav. 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