Therapeutic potential for KCC2-targeted neurological diseases
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 th...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Japanese Dental Science Review |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1882761623000376 |
| _version_ | 1797387900045754368 |
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| author | Kazuo Tomita Yoshikazu Kuwahara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Yuko Takashi Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Akihiro Kurimasa Yoshihiro Nishitani Tomoaki Sato |
| author_facet | Kazuo Tomita Yoshikazu Kuwahara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Yuko Takashi Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Akihiro Kurimasa Yoshihiro Nishitani Tomoaki Sato |
| author_sort | Kazuo Tomita |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:31:48Z |
| format | Article |
| id | doaj.art-e727f14819824679bcf66fd6b2e36fd6 |
| institution | Directory Open Access Journal |
| issn | 1882-7616 |
| language | English |
| last_indexed | 2024-03-08T22:31:48Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Japanese Dental Science Review |
| spelling | doaj.art-e727f14819824679bcf66fd6b2e36fd62023-12-18T04:24:10ZengElsevierJapanese Dental Science Review1882-76162023-12-0159431438Therapeutic potential for KCC2-targeted neurological diseasesKazuo Tomita0Yoshikazu Kuwahara1Kento Igarashi2Junichi Kitanaka3Nobue Kitanaka4Yuko Takashi5Koh-ichi Tanaka6Mehryar Habibi Roudkenar7Amaneh Mohammadi Roushandeh8Akihiro Kurimasa9Yoshihiro Nishitani10Tomoaki Sato11Department 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; Corresponding author at: Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890–8544, Japan.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, JapanDepartment 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, JapanLaboratory of Drug Addiction and Experimental Therapeutics, Schoolof Pharmacy, Hyogo Medical University, Hyogo 650-8530, JapanLaboratory 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, JapanDepartment of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890–8544, JapanDepartment 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, JapanDepartment 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, IranDepartment of Anatomy, School of Biomedical Sciences, Medicine & Health, UNSW Sydney, Sydney, NSW 2052, AustraliaDivision of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, 983-8536, JapanDepartment of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890–8544, JapanDepartment of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890–8544, Japan; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1882761623000376KCC2GABANeurological diseasesInflammationTherapeutic target |
| spellingShingle | Kazuo Tomita Yoshikazu Kuwahara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Yuko Takashi Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Akihiro Kurimasa Yoshihiro Nishitani Tomoaki Sato Therapeutic potential for KCC2-targeted neurological diseases Japanese Dental Science Review KCC2 GABA Neurological diseases Inflammation Therapeutic target |
| title | Therapeutic potential for KCC2-targeted neurological diseases |
| title_full | Therapeutic potential for KCC2-targeted neurological diseases |
| title_fullStr | Therapeutic potential for KCC2-targeted neurological diseases |
| title_full_unstemmed | Therapeutic potential for KCC2-targeted neurological diseases |
| title_short | Therapeutic potential for KCC2-targeted neurological diseases |
| title_sort | therapeutic potential for kcc2 targeted neurological diseases |
| topic | KCC2 GABA Neurological diseases Inflammation Therapeutic target |
| url | http://www.sciencedirect.com/science/article/pii/S1882761623000376 |
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