A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models
| العنوان: | A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models |
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| المؤلفون: | Nicholas D. E. Greene, Joseph Damstra-Oddy, Joanna Boberska, Robert J. Harvey, Paul Finch, Amy Joy Baldwin, Christopher J. Perry, Christopher R. L. Thompson, Fabiana Piscitelli, Adrian J. Harwood, Kit-Yi Leung, Eleanor C. Warren, Robin S.B. Williams, Benjamin J. Whalley, Balint Stewart, Alister J. McNeish, Annette Müller-Taubenberger, Claire M. Williams, Devdutt Sharma, Sarah Glyn, Sandrine P. Claus, Pabitra Hriday Patra |
| المصدر: | British journal of pharmacology (Online) (2020). info:cnr-pdr/source/autori:Perry CJ, Finch P, Müller-Taubenberger A, Leung KY, Warren EC, Damstra-Oddy J, Sharma D, Patra PH, Glyn S, Boberska J, Stewart B, Baldwin A, Piscitelli F, Harvey RJ, Harwood A, Thompson C, Claus S, Greene NDE, McNeish A, Williams CM, Whalley BJ, Williams RSB./titolo:A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models./doi:/rivista:British journal of pharmacology (Online)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume Perry, C J, Finch, P, Müller-Taubenberger, A, Leung, K-Y, Warren, E C, Damstra-Oddy, J, Sharma, D, Patra, P H, Glyn, S, Boberska, J, Stewart, B, Baldwin, A, Piscitelli, F, Harvey, R J, Harwood, A, Thompson, C, Claus, S, Greene, N D E, McNeish, A, Williams, C M, Whalley, B J & Williams, R S B 2019, ' A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models ', British Journal of Pharmacology . https://doi.org/10.1111/bph.14892Test British Journal of Pharmacology |
| بيانات النشر: | Nature Publishing Group., Basingstoke, Regno Unito, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Dictyostelium discoideum, Carbon Cycle, 03 medical and health sciences, chemistry.chemical_compound, cannabidiol, Methionine, 0302 clinical medicine, Dravet syndrome, medicine, Animals, Humans, Dictyostelium, Methionine synthase, Pharmacology, Epilepsy, Glycine cleavage system, biology, Lennox Gastaut Syndrome, biology.organism_classification, medicine.disease, Research Papers, Rats, Cell biology, 030104 developmental biology, Mechanism of action, chemistry, biology.protein, Anticonvulsants, medicine.symptom, Cannabidiol, 030217 neurology & neurosurgery, Research Paper, medicine.drug |
| الوصف: | Background and Purpose: Epidiolex, a form of highly purified cannabidiol (CBD) derived from Cannabis plants has demonstrated seizure control activity in patients with Dravet syndrome, without a fully elucidated mechanism of action. We have employed an unbiased approach to investigate this mechanism at a cellular level.\ud Experimental Approach: We use a tractable biomedical model organism, Dictyostelium, to identify protein controlling the effect of CBD and characterize this mechanism. We then translate these results to a Dravet Syndrome mouse model and an acute in vitro seizure model.\ud Key Results: CBD activity is partially dependent upon the mitochondrial glycine cleavage system component, GcvH1 in Dictyostelium, orthologous to the human GCSH protein, which is functionally linked to folate one-carbon metabolism (FOCM). Analysis of FOCM components identified a mechanism for CBD in directly inhibiting methionine synthesis. Analysis of brain tissue from a Dravet syndrome mouse model also showed drastically altered levels of one-carbon components including methionine, and an in vitro rat seizure model showed an elevated level of methionine that is attenuated following CBD treatment. \ud Conclusions and Implications: Our results suggest a novel mechanism for CBD in the regulating methionine levels, and identify altered one-carbon metabolism in Dravet syndrome and seizure activity.\ud voltage-dependent anion selective channel proteins, VDAC1. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0007-1188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3a90729a06a68fac2f2a4686eb515ddTest https://publications.cnr.it/doc/411516Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c3a90729a06a68fac2f2a4686eb515dd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00071188 |
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