亨廷顿氏病的 Neurexin1 水平以及 Neurexin1 在疾病进展过程中的减少。

IF 2.4 4区 医学 Q3 NEUROSCIENCES
Kyoungjoo Cho, Gyung Whan Kim
{"title":"亨廷顿氏病的 Neurexin1 水平以及 Neurexin1 在疾病进展过程中的减少。","authors":"Kyoungjoo Cho, Gyung Whan Kim","doi":"10.1016/j.neures.2024.10.006","DOIUrl":null,"url":null,"abstract":"<p><p>Huntington's disease (HD) is a neurodegenerative disorder characterized by the presence of abnormally expanded polyglutamine tracts in huntingtin protein (HTT). Mutant HTT disrupts synaptic transmission and plasticity, particularly in the striatum and cortex, leading to early dysfunctions, such as altered neurotransmitter release, impaired synaptic vesicle recycling, and disrupted postsynaptic receptor function. Synaptic loss precedes neuronal degeneration and contributes to disease progression. Neurexin1 (NRXN1), a synaptic cell adhesion molecule primarily located in the presynaptic membrane, plays a crucial role in maintaining synaptic integrity. The present study investigated the role of NRXN1 in HD. This study researched whether the changed level has been related to expanded polyQ stretch and disease progression. Here, we report a reduction in NRXN1 levels in post-symptomatic HD mice and in neuronal cells expressing abnormally expanded polyQ tracts. Mutant HTT was found to decrease NRXN1 levels while increasing LAMP2A levels, which promotes lysosomal degradation of NRXN1. In HD cells expressing Q111, downregulated LAMP2A restored NRXN1 levels and maintained cell proliferation compared with cells expressing Q7. These findings suggest that NRXN1 is regulated by LAMP2A-mediated way and that decreased NRXN1 levels are associated with symptomatic progression and neuronal cell loss in HD.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neurexin1 level in Huntington's Disease and decreased Neurexin1 in disease progression.\",\"authors\":\"Kyoungjoo Cho, Gyung Whan Kim\",\"doi\":\"10.1016/j.neures.2024.10.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Huntington's disease (HD) is a neurodegenerative disorder characterized by the presence of abnormally expanded polyglutamine tracts in huntingtin protein (HTT). Mutant HTT disrupts synaptic transmission and plasticity, particularly in the striatum and cortex, leading to early dysfunctions, such as altered neurotransmitter release, impaired synaptic vesicle recycling, and disrupted postsynaptic receptor function. Synaptic loss precedes neuronal degeneration and contributes to disease progression. Neurexin1 (NRXN1), a synaptic cell adhesion molecule primarily located in the presynaptic membrane, plays a crucial role in maintaining synaptic integrity. The present study investigated the role of NRXN1 in HD. This study researched whether the changed level has been related to expanded polyQ stretch and disease progression. Here, we report a reduction in NRXN1 levels in post-symptomatic HD mice and in neuronal cells expressing abnormally expanded polyQ tracts. Mutant HTT was found to decrease NRXN1 levels while increasing LAMP2A levels, which promotes lysosomal degradation of NRXN1. In HD cells expressing Q111, downregulated LAMP2A restored NRXN1 levels and maintained cell proliferation compared with cells expressing Q7. These findings suggest that NRXN1 is regulated by LAMP2A-mediated way and that decreased NRXN1 levels are associated with symptomatic progression and neuronal cell loss in HD.</p>\",\"PeriodicalId\":19146,\"journal\":{\"name\":\"Neuroscience Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroscience Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.neures.2024.10.006\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.neures.2024.10.006","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

亨廷顿氏病(Huntington's disease,HD)是一种神经退行性疾病,其特征是亨廷丁蛋白(HTT)中存在异常扩展的多谷氨酰胺束。突变型 HTT 会破坏突触传递和可塑性,尤其是在纹状体和大脑皮层,导致早期功能障碍,如神经递质释放改变、突触囊泡循环受损和突触后受体功能紊乱。突触丧失先于神经元变性,并导致疾病进展。Neurexin1(NRXN1)是一种主要位于突触前膜的突触细胞粘附分子,在维持突触完整性方面起着至关重要的作用。本研究探讨了 NRXN1 在 HD 中的作用。本研究探讨了NRXN1水平的变化是否与polyQ伸展扩大和疾病进展有关。在此,我们报告了有症状后的 HD 小鼠和表达异常扩展的 polyQ 束的神经元细胞中 NRXN1 水平的降低。研究发现,突变 HTT 会降低 NRXN1 的水平,同时增加 LAMP2A 的水平,而 LAMP2A 会促进 NRXN1 的溶酶体降解。在表达 Q111 的 HD 细胞中,与表达 Q7 的细胞相比,下调 LAMP2A 可恢复 NRXN1 的水平并维持细胞增殖。这些研究结果表明,NRXN1受LAMP2A介导的方式调节,NRXN1水平的降低与HD的症状进展和神经细胞丢失有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neurexin1 level in Huntington's Disease and decreased Neurexin1 in disease progression.

Huntington's disease (HD) is a neurodegenerative disorder characterized by the presence of abnormally expanded polyglutamine tracts in huntingtin protein (HTT). Mutant HTT disrupts synaptic transmission and plasticity, particularly in the striatum and cortex, leading to early dysfunctions, such as altered neurotransmitter release, impaired synaptic vesicle recycling, and disrupted postsynaptic receptor function. Synaptic loss precedes neuronal degeneration and contributes to disease progression. Neurexin1 (NRXN1), a synaptic cell adhesion molecule primarily located in the presynaptic membrane, plays a crucial role in maintaining synaptic integrity. The present study investigated the role of NRXN1 in HD. This study researched whether the changed level has been related to expanded polyQ stretch and disease progression. Here, we report a reduction in NRXN1 levels in post-symptomatic HD mice and in neuronal cells expressing abnormally expanded polyQ tracts. Mutant HTT was found to decrease NRXN1 levels while increasing LAMP2A levels, which promotes lysosomal degradation of NRXN1. In HD cells expressing Q111, downregulated LAMP2A restored NRXN1 levels and maintained cell proliferation compared with cells expressing Q7. These findings suggest that NRXN1 is regulated by LAMP2A-mediated way and that decreased NRXN1 levels are associated with symptomatic progression and neuronal cell loss in HD.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Neuroscience Research
Neuroscience Research 医学-神经科学
CiteScore
5.60
自引率
3.40%
发文量
136
审稿时长
28 days
期刊介绍: The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信