The Role of Adenosine Tone and Adenosine Receptors in Huntington's Disease.

IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Journal of Caffeine and Adenosine Research Pub Date : 2018-06-01 DOI:10.1089/caff.2018.0006
David Blum, Yijuang Chern, Maria Rosaria Domenici, Luc Buée, Chien-Yu Lin, William Rea, Sergi Ferré, Patrizia Popoli
{"title":"The Role of Adenosine Tone and Adenosine Receptors in Huntington's Disease.","authors":"David Blum, Yijuang Chern, Maria Rosaria Domenici, Luc Buée, Chien-Yu Lin, William Rea, Sergi Ferré, Patrizia Popoli","doi":"10.1089/caff.2018.0006","DOIUrl":null,"url":null,"abstract":"<p><p>Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a mutation in the IT15 gene that encodes for the huntingtin protein. Mutated hungtingtin, although widely expressed in the brain, predominantly affects striato-pallidal neurons, particularly enriched with adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>R), suggesting a possible involvement of adenosine and A<sub>2A</sub>R is the pathogenesis of HD. In fact, polymorphic variation in the <i>ADORA2A</i> gene influences the age at onset in HD, and A<sub>2A</sub>R dynamics is altered by mutated huntingtin. Basal levels of adenosine and adenosine receptors are involved in many processes critical for neuronal function and homeostasis, including modulation of synaptic activity and excitotoxicity, the control of neurotrophin levels and functions, and the regulation of protein degradation mechanisms. In the present review, we critically analyze the current literature involving the effect of altered adenosine tone and adenosine receptors in HD and discuss why therapeutics that modulate the adenosine system may represent a novel approach for the treatment of HD.</p>","PeriodicalId":15112,"journal":{"name":"Journal of Caffeine and Adenosine Research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049521/pdf/caff.2018.0006.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Caffeine and Adenosine Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/caff.2018.0006","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0

Abstract

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a mutation in the IT15 gene that encodes for the huntingtin protein. Mutated hungtingtin, although widely expressed in the brain, predominantly affects striato-pallidal neurons, particularly enriched with adenosine A2A receptors (A2AR), suggesting a possible involvement of adenosine and A2AR is the pathogenesis of HD. In fact, polymorphic variation in the ADORA2A gene influences the age at onset in HD, and A2AR dynamics is altered by mutated huntingtin. Basal levels of adenosine and adenosine receptors are involved in many processes critical for neuronal function and homeostasis, including modulation of synaptic activity and excitotoxicity, the control of neurotrophin levels and functions, and the regulation of protein degradation mechanisms. In the present review, we critically analyze the current literature involving the effect of altered adenosine tone and adenosine receptors in HD and discuss why therapeutics that modulate the adenosine system may represent a novel approach for the treatment of HD.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
腺苷激素和腺苷受体在亨廷顿氏症中的作用。
亨廷顿氏病(Huntington's disease,HD)是一种遗传性神经退行性疾病,由编码亨廷丁蛋白的 IT15 基因突变引起。变异的亨廷廷蛋白虽然在大脑中广泛表达,但主要影响纹状体-苍白球神经元,尤其是富含腺苷 A2A 受体(A2AR)的神经元,这表明腺苷和 A2AR 可能参与了 HD 的发病机制。事实上,ADORA2A基因的多态性变异会影响HD的发病年龄,而A2AR的动态变化会因突变的亨廷蛋白而改变。腺苷和腺苷受体的基础水平参与了许多对神经元功能和稳态至关重要的过程,包括突触活动和兴奋毒性的调节、神经营养素水平和功能的控制以及蛋白质降解机制的调节。在本综述中,我们对涉及 HD 中腺苷张力和腺苷受体改变的影响的现有文献进行了批判性分析,并讨论了为什么调节腺苷系统的疗法可能是治疗 HD 的一种新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
An Interview with John Salamone Correction to: Kinetic and Dynamic Description of Caffeine by Alsabri et al. J Caffeine Adenosine Res 2018;8(1): 3-9; DOI: 10.1089/caff.2017.0011. The Closing of a Chapter Catching Up with David Blum Caffeine Delays Parasympathetic Reactivation After a High-Intensity Intermittent Exercise in Handball Players
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1