IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia
α6-containing GABAA receptors (α6GABAARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavi...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000386 |
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| author | Lih-Chu Chiou Werner Sieghart |
| author_facet | Lih-Chu Chiou Werner Sieghart |
| author_sort | Lih-Chu Chiou |
| collection | DOAJ |
| description | α6-containing GABAA receptors (α6GABAARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavior. Activation of α6GABAARs enhances the precision of sensory inputs, enables rapid and coordinated movement and adequate responses to the environment, and protects the brain from information overflow. The cerebellum has strong connections to multiple brain regions via closed loop circuits and is also extensively connected with the dopamine system in the prefrontal cortex, that initiates the execution of behavior. Patients suffering from schizophrenia exhibit an impaired structure and function of the cerebellum and an impaired GABAergic transmission at α6GABAARs. This also impairs the function of the dopamine system, can explain a variety of schizophrenia symptoms observed, and might be one of the pathophysiological causes of schizophrenia. Enhancing GABAergic transmission at α6GABAARs should thus reduce the symptoms of schizophrenia. This recently has been confirmed by demonstrating that positive allosteric modulators with high selectivity for α6GABAARs can reduce positive and negative symptoms and cognitive impairment of schizophrenia in several animal models of this disorder. So far, the beneficial actions of these modulators have been demonstrated in animal models of neuropsychiatric disorders, only. Future human studies have to investigate the safety and possible side effects of these modulators and to clarify, to which extent individual symptoms of schizophrenia can be reduced by these drugs in patients during acute and chronic dosing. |
| format | Article |
| id | doaj-art-8d6ef38b3b254e31b92436e11f3820fd |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-8d6ef38b3b254e31b92436e11f3820fd2025-02-07T04:46:53ZengElsevierPharmacological Research1096-11862025-03-01213107613IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophreniaLih-Chu Chiou0Werner Sieghart1Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, TaiwanCenter for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Vienna, Austria; Correspondence to: Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Spitalgasse 4, Vienna A-1090, Austria.α6-containing GABAA receptors (α6GABAARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavior. Activation of α6GABAARs enhances the precision of sensory inputs, enables rapid and coordinated movement and adequate responses to the environment, and protects the brain from information overflow. The cerebellum has strong connections to multiple brain regions via closed loop circuits and is also extensively connected with the dopamine system in the prefrontal cortex, that initiates the execution of behavior. Patients suffering from schizophrenia exhibit an impaired structure and function of the cerebellum and an impaired GABAergic transmission at α6GABAARs. This also impairs the function of the dopamine system, can explain a variety of schizophrenia symptoms observed, and might be one of the pathophysiological causes of schizophrenia. Enhancing GABAergic transmission at α6GABAARs should thus reduce the symptoms of schizophrenia. This recently has been confirmed by demonstrating that positive allosteric modulators with high selectivity for α6GABAARs can reduce positive and negative symptoms and cognitive impairment of schizophrenia in several animal models of this disorder. So far, the beneficial actions of these modulators have been demonstrated in animal models of neuropsychiatric disorders, only. Future human studies have to investigate the safety and possible side effects of these modulators and to clarify, to which extent individual symptoms of schizophrenia can be reduced by these drugs in patients during acute and chronic dosing.http://www.sciencedirect.com/science/article/pii/S1043661825000386α6-containing GABAA receptorsPositive modulators selective for α6-containing GABAA receptorsCerebellar granule cellsCerebellar function in the brainSchizophreniaNeuropsychiatric disorders |
| spellingShingle | Lih-Chu Chiou Werner Sieghart IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia Pharmacological Research α6-containing GABAA receptors Positive modulators selective for α6-containing GABAA receptors Cerebellar granule cells Cerebellar function in the brain Schizophrenia Neuropsychiatric disorders |
| title | IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia |
| title_full | IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia |
| title_fullStr | IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia |
| title_full_unstemmed | IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia |
| title_short | IUPHAR Review: Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia |
| title_sort | iuphar review alpha6 containing gabaa receptors novel targets for the treatment of schizophrenia |
| topic | α6-containing GABAA receptors Positive modulators selective for α6-containing GABAA receptors Cerebellar granule cells Cerebellar function in the brain Schizophrenia Neuropsychiatric disorders |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000386 |
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