Therapeutic potential for KCC2-targeted neurological diseases.

Autor:	Tomita K; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo 650-8530, Japan., Kuwahara Y; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, 983-8536, Japan., Igarashi K; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo 650-8530, Japan., Kitanaka J; Laboratory of Drug Addiction and Experimental Therapeutics, Schoolof Pharmacy, Hyogo Medical University, Hyogo 650-8530, Japan., Kitanaka N; Laboratory of Drug Addiction and Experimental Therapeutics, Schoolof Pharmacy, Hyogo Medical University, Hyogo 650-8530, Japan.; Department of Pharmacology, School of Medicine, Hyogo Medical University, Hyogo 663-8501, Japan., Takashi Y; Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan., Tanaka KI; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo 650-8530, Japan., Roudkenar MH; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.; Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht 41937-13194, Iran., Roushandeh AM; Department of Anatomy, School of Biomedical Sciences, Medicine & Health, UNSW Sydney, Sydney, NSW 2052, Australia., Kurimasa A; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, 983-8536, Japan., Nishitani Y; Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan., Sato T; Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
Jazyk:	angličtina
Zdroj:	The Japanese dental science review [Jpn Dent Sci Rev] 2023 Dec; Vol. 59, pp. 431-438. Date of Electronic Publication: 2023 Nov 11.
DOI:	10.1016/j.jdsr.2023.11.001
Abstrakt:	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. However, since the pathogenesis of these diseases is not yet fully investigated, drug therapy is still limited to symptomatic therapy. Targeting KCC2, which is mainly expressed in the brain, seems to be an appropriate approach in the treatment of these diseases. In this review, we aimed to discuss about stress and inflammation, KCC2 and Gamma-aminobutyric acid (GABA) function, diseases which decrease the KCC2 levels in the brain, factors that regulate KCC2 activity, and the possibility to overcome neuronal dysfunction targeting KCC2. We also aimed to discuss the relationships between neurological diseases and LPS caused by Porphyromonas gingivalis ( P. g ), which is a type of oral bacterium. Clinical trials on oxytocin, sirtuin 1 (SIRT1) activator, and transient receptor potential cation channel subfamily V Member 1 activator have been conducted to develop effective treatment methods. We believe that KCC2 modulators that regulate mitochondria, such as oxytocin, glycogen synthase kinase 3β (GSK3β), and SIRT1, can be potential targets for neurological diseases. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.)
Databáze:	MEDLINE
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