{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:07:28Z","timestamp":1791083248410,"version":"4.1.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,10,10]]},"abstract":"<jats:p>Introduction: Tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, coded by KCNK13) provides an upstream regulation of the activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which has been suggested as one of the key mechanisms of the pathological process in neurodegeneration mainly from in vitro and in vivo model systems studies. However, unequivocal evidence from neurodegenerative disorders has been lacking. Objective: To investigate the involvement of the THIK-1\/NLRP3 pathway in the pathological process of Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD). Methods: This study investigated gene expression of markers in the THIK-1\/NLRP3 pathway in an animal model representing AD as well as in human postmortem brains of AD and PD by quantitative real-time PCR. THIK-1 protein expression was determined using automated capillary electrophoresis immunoblotting. Furthermore, DNA methylation of KCNK13 was analysed in AD cohort by pyrosequencing. Results: A substantial upregulation of KCNK13, glial activation markers, NLRP3 inflammasome components, and IL1B was observed in the animal study. Increased expression of KCNK13 support an inflammatory glial cell activation in both advanced AD and PD. The increase in KCNK13 expression was also supported by downregulation in DNA methylation of KCNK13 in AD. Conclusions: The association between THIK-1 K+ channels expression and pathology changes indicates a THIK-1-induced activation of this glial subtype in AD and PD. Therefore, specific blocks of the microglial THIK-1 K+ channels at the early stage of AD and PD may be beneficial for the patients.<\/jats:p>","DOI":"10.3233\/jad-230616","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T13:43:25Z","timestamp":1694526205000},"page":"1757-1769","source":"Crossref","is-referenced-by-count":13,"title":["Elevated Expression of Two Pore Potassium Channel THIK-1 in Alzheimer\u2019s Disease: An Inflammatory Mechanism"],"prefix":"10.1177","volume":"95","author":[{"given":"Hao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Yunnan Province, Kunming, China"},{"name":"Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of 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