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Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease.

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Title: Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease.
Authors: Xiong, Wei, Chen, Shao-Rui, He, Liming, Cheng, Kejun, Zhao, Yi-Lin, Chen, Hong, Li, De-Pei, Homanics, Gregg E, Peever, John, Rice, Kenner C, Wu, Ling-gang, Pan, Hui-Lin, Zhang, Li
Source: Nature Neuroscience. Feb2014, Vol. 17 Issue 2, p232-239. 8p. 6 Graphs.
Subjects: Glycine receptors, Presynaptic receptors, Glycine, Dehydration reactions, Cannabinoids
Abstract: Although postsynaptic glycine receptors (GlyRs) as αβ heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing point mutations in α1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease. The GlyRs expressed as α1 homomers either in HEK-293 cells or at presynaptic terminals of the calyceal synapses in the auditory brainstem are more vulnerable than heteromers to hyperekplexia mutation-induced impairment. Homomeric mutants are more sensitive to DH-CBD than are heteromers, suggesting presynaptic GlyRs as a primary target. Consistent with this idea, DH-CBD selectively rescues impaired presynaptic GlyR activity and diminished glycine release in the brainstem and spinal cord of hyperekplexic mutant mice. Thus, presynaptic α1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease.
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  Data: <searchLink fieldCode="AR" term="%22Xiong%2C+Wei%22">Xiong, Wei</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Shao-Rui%22">Chen, Shao-Rui</searchLink><br /><searchLink fieldCode="AR" term="%22He%2C+Liming%22">He, Liming</searchLink><br /><searchLink fieldCode="AR" term="%22Cheng%2C+Kejun%22">Cheng, Kejun</searchLink><br /><searchLink fieldCode="AR" term="%22Zhao%2C+Yi-Lin%22">Zhao, Yi-Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Hong%22">Chen, Hong</searchLink><br /><searchLink fieldCode="AR" term="%22Li%2C+De-Pei%22">Li, De-Pei</searchLink><br /><searchLink fieldCode="AR" term="%22Homanics%2C+Gregg+E%22">Homanics, Gregg E</searchLink><br /><searchLink fieldCode="AR" term="%22Peever%2C+John%22">Peever, John</searchLink><br /><searchLink fieldCode="AR" term="%22Rice%2C+Kenner+C%22">Rice, Kenner C</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Ling-gang%22">Wu, Ling-gang</searchLink><br /><searchLink fieldCode="AR" term="%22Pan%2C+Hui-Lin%22">Pan, Hui-Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Li%22">Zhang, Li</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. Feb2014, Vol. 17 Issue 2, p232-239. 8p. 6 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Glycine+receptors%22">Glycine receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Presynaptic+receptors%22">Presynaptic receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Glycine%22">Glycine</searchLink><br /><searchLink fieldCode="DE" term="%22Dehydration+reactions%22">Dehydration reactions</searchLink><br /><searchLink fieldCode="DE" term="%22Cannabinoids%22">Cannabinoids</searchLink>
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  Label: Abstract
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  Data: Although postsynaptic glycine receptors (GlyRs) as αβ heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing point mutations in α1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease. The GlyRs expressed as α1 homomers either in HEK-293 cells or at presynaptic terminals of the calyceal synapses in the auditory brainstem are more vulnerable than heteromers to hyperekplexia mutation-induced impairment. Homomeric mutants are more sensitive to DH-CBD than are heteromers, suggesting presynaptic GlyRs as a primary target. Consistent with this idea, DH-CBD selectively rescues impaired presynaptic GlyR activity and diminished glycine release in the brainstem and spinal cord of hyperekplexic mutant mice. Thus, presynaptic α1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Feb2014
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