• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

酪氨酸突变的腺相关病毒2介导的PTEN基因短发夹RNA沉默促进成年视神经轴突再生。

Tyrosine-mutated AAV2-mediated shRNA silencing of PTEN promotes axon regeneration of adult optic nerve.

作者信息

Huang ZhengRu, Hu ZiZhong, Xie Ping, Liu QingHuai

机构信息

Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Department of Ophthalmology, the Second People´s Hospital of Changshu, Changshu, Jiangsu Province, China.

出版信息

PLoS One. 2017 Mar 21;12(3):e0174096. doi: 10.1371/journal.pone.0174096. eCollection 2017.

DOI:10.1371/journal.pone.0174096
PMID:28323869
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5360277/
Abstract

Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm. We found that mutant AAV2 displayed higher infection efficiency to RGCs and Müller cells by intravitreal injection, mediated PTEN suppression, resulted in much more RGCs survival and more robust axons regeneration compared with wild type AAV2, due to the different extent of the mTOR complex-1 activation and glutamate aspartate transporter (GLAST) regulation. These results suggest that high efficiency AAV2-mediated PTEN knockdown represents a practicable therapeutic strategy for optic neuropathy.

摘要

通过缺失磷酸酶和张力蛋白同源物（PTEN）激活PI3K/AKT/mTOR信号通路已被证实可增强神经元的内在生长能力，以促进损伤后中枢神经系统轴突的再生。考虑到目前临床实践中尚无条件性基因缺失技术，我们利用衣壳残基酪氨酸444突变为苯丙氨酸的单链2型腺相关病毒（AAV2）作为载体，递送短发夹RNA以沉默PTEN，从而在成年大鼠视神经切断模型中促进视网膜神经节细胞（RGCs）的存活和轴突再生。我们发现，通过玻璃体内注射，突变型AAV2对RGCs和 Müller细胞具有更高的感染效率，介导PTEN抑制，与野生型AAV2相比，由于mTOR复合物1激活和谷氨酸天冬氨酸转运体（GLAST）调节程度不同，导致更多的RGCs存活和更强有力的轴突再生。这些结果表明，高效AAV2介导的PTEN敲低是一种可行的视神经病变治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/c0fe770a81a7/pone.0174096.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/900c3e9e6599/pone.0174096.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/77b148c6cf6b/pone.0174096.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/3cdd64d650a2/pone.0174096.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/56d83847272a/pone.0174096.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/e8a008177337/pone.0174096.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/5c59d9a443e6/pone.0174096.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/12d34febc520/pone.0174096.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/7dd845bce1a5/pone.0174096.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/76895a4fd332/pone.0174096.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/c8e63a84417c/pone.0174096.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/c0fe770a81a7/pone.0174096.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/900c3e9e6599/pone.0174096.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/77b148c6cf6b/pone.0174096.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/3cdd64d650a2/pone.0174096.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/56d83847272a/pone.0174096.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/e8a008177337/pone.0174096.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/5c59d9a443e6/pone.0174096.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/12d34febc520/pone.0174096.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/7dd845bce1a5/pone.0174096.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/76895a4fd332/pone.0174096.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/c8e63a84417c/pone.0174096.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a5/5360277/c0fe770a81a7/pone.0174096.g011.jpg

相似文献

1
Tyrosine-mutated AAV2-mediated shRNA silencing of PTEN promotes axon regeneration of adult optic nerve.酪氨酸突变的腺相关病毒2介导的PTEN基因短发夹RNA沉默促进成年视神经轴突再生。
PLoS One. 2017 Mar 21;12(3):e0174096. doi: 10.1371/journal.pone.0174096. eCollection 2017.
2
PTEN knockdown with the Y444F mutant AAV2 vector promotes axonal regeneration in the adult optic nerve.使用Y444F突变型腺相关病毒2型载体敲低PTEN可促进成年视神经的轴突再生。
Neural Regen Res. 2018 Jan;13(1):135-144. doi: 10.4103/1673-5374.224381.
3
Lab review: Molecular dissection of the signal transduction pathways associated with PTEN deletion-induced optic nerve regeneration.实验室综述：与 PTEN 缺失诱导的视神经再生相关的信号转导通路的分子剖析。
Restor Neurol Neurosci. 2019;37(6):545-552. doi: 10.3233/RNN-190949.
4
Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway.通过调节PTEN/mTOR信号通路促进成体中枢神经系统中的轴突再生。
Science. 2008 Nov 7;322(5903):963-6. doi: 10.1126/science.1161566.
5
Viral vector-based improvement of optic nerve regeneration: characterization of individual axons' growth patterns and synaptogenesis in a visual target.基于病毒载体对视神经再生的改善：视觉靶标中单个轴突生长模式和突触形成的特征
Gene Ther. 2015 Oct;22(10):811-21. doi: 10.1038/gt.2015.51. Epub 2015 May 25.
6
Interleukin-6 contributes to CNS axon regeneration upon inflammatory stimulation.白细胞介素-6 有助于炎症刺激后的中枢神经系统轴突再生。
Cell Death Dis. 2013 Apr 25;4(4):e609. doi: 10.1038/cddis.2013.126.
7
HDAC5 promotes optic nerve regeneration by activating the mTOR pathway.HDAC5 通过激活 mTOR 通路促进视神经再生。
Exp Neurol. 2019 Jul;317:271-283. doi: 10.1016/j.expneurol.2019.03.011. Epub 2019 Mar 22.
8
Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury.上调 Lin28a 促进视神经和脊髓损伤成年小鼠的轴突再生。
Mol Ther. 2020 Aug 5;28(8):1902-1917. doi: 10.1016/j.ymthe.2020.04.010. Epub 2020 Apr 15.
9
Sphingosine 1-phosphate receptor 1 is required for retinal ganglion cell survival after optic nerve trauma.1-磷酸鞘氨醇受体1是视神经损伤后视网膜神经节细胞存活所必需的。
J Neurochem. 2016 Aug;138(4):571-86. doi: 10.1111/jnc.13701. Epub 2016 Jul 6.
10
Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion.单核细胞衍生的基质细胞衍生因子 1 支持视神经再生，并改变视网膜神经节细胞对 Pten 缺失的反应。
Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2113751119. doi: 10.1073/pnas.2113751119. Epub 2022 Apr 8.

引用本文的文献

1
Lipid nanoparticle technology-mediated therapeutic gene manipulation in the eyes.脂质纳米颗粒技术介导的眼部治疗性基因操控
Mol Ther Nucleic Acids. 2024 Jun 3;35(3):102236. doi: 10.1016/j.omtn.2024.102236. eCollection 2024 Sep 10.
2
Adeno-associated virus mediated gene therapy for neuroprotection of retinal ganglion cells in glaucoma.腺相关病毒介导的基因治疗在青光眼的视网膜神经节细胞保护中的应用。
Vision Res. 2023 May;206:108196. doi: 10.1016/j.visres.2023.108196. Epub 2023 Feb 20.
3
Degeneration of retina-brain components and connections in glaucoma: Disease causation and treatment options for eyesight preservation.

本文引用的文献

1
mTORC1 is necessary but mTORC2 and GSK3β are inhibitory for AKT3-induced axon regeneration in the central nervous system.mTORC1是必要的，但mTORC2和GSK3β对中枢神经系统中AKT3诱导的轴突再生具有抑制作用。
Elife. 2016 Mar 30;5:e14908. doi: 10.7554/eLife.14908.
2
Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve.水通道蛋白4通道抑制对视神经挤压后视网膜神经节细胞存活及谷氨酸代谢的负面影响
Exp Eye Res. 2016 May;146:118-127. doi: 10.1016/j.exer.2015.12.012. Epub 2016 Jan 7.
3
Viral vector-based improvement of optic nerve regeneration: characterization of individual axons' growth patterns and synaptogenesis in a visual target.
青光眼患者视网膜-脑组成部分及连接的退化：疾病成因与视力保护的治疗选择
Curr Res Neurobiol. 2022 Jun 9;3:100037. doi: 10.1016/j.crneur.2022.100037. eCollection 2022.
4
Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis.双敲除 PI3K 和 PTEN 可改变晶状体出生后的生长和稳态。
Cells. 2022 Aug 30;11(17):2708. doi: 10.3390/cells11172708.
5
BMP4/Smad1 Signalling Promotes Spinal Dorsal Column Axon Regeneration and Functional Recovery After Injury.BMP4/Smad1 信号促进损伤后脊髓背柱轴突的再生和功能恢复。
Mol Neurobiol. 2019 Oct;56(10):6807-6819. doi: 10.1007/s12035-019-1555-9. Epub 2019 Mar 28.
6
Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression.电针通过降低PTEN和p53表达恢复小鼠脊髓损伤后的运动功能
Front Mol Neurosci. 2018 Nov 16;11:411. doi: 10.3389/fnmol.2018.00411. eCollection 2018.
7
Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection.Shp2 缺失可挽救 BDNF/TrkB 信号转导，并有助于改善视网膜神经节细胞的神经保护。
Mol Ther. 2019 Feb 6;27(2):424-441. doi: 10.1016/j.ymthe.2018.09.019. Epub 2018 Oct 4.
8
Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair.新型多药物递送水凝胶利用瘢痕归巢脂质体改善脊髓损伤修复。
Theranostics. 2018 Aug 7;8(16):4429-4446. doi: 10.7150/thno.26717. eCollection 2018.
9
Lentivirus-Mediated Overexpression of miR-29a Promotes Axonal Regeneration and Functional Recovery in Experimental Spinal Cord Injury via PI3K/Akt/mTOR Pathway.慢病毒介导的 miR-29a 过表达通过 PI3K/Akt/mTOR 通路促进实验性脊髓损伤后的轴突再生和功能恢复。
Neurochem Res. 2018 Nov;43(11):2038-2046. doi: 10.1007/s11064-018-2625-5. Epub 2018 Sep 1.
10
PTEN-GSK3β-MOB1 axis controls neurite outgrowth in vitro and in vivo.PTEN-GSK3β-MOB1 轴控制体外和体内的神经突生长。
Cell Mol Life Sci. 2018 Dec;75(23):4445-4464. doi: 10.1007/s00018-018-2890-0. Epub 2018 Aug 1.
基于病毒载体对视神经再生的改善：视觉靶标中单个轴突生长模式和突触形成的特征
Gene Ther. 2015 Oct;22(10):811-21. doi: 10.1038/gt.2015.51. Epub 2015 May 25.
4
AAVshRNA-mediated suppression of PTEN in adult rats in combination with salmon fibrin administration enables regenerative growth of corticospinal axons and enhances recovery of voluntary motor function after cervical spinal cord injury.腺相关病毒短发夹 RNA 介导的成年大鼠 PTEN 抑制与鲑鱼纤维蛋白联合给药可促进皮质脊髓束轴突的再生性生长，并增强颈脊髓损伤后自主运动功能的恢复。
J Neurosci. 2014 Jul 23;34(30):9951-62. doi: 10.1523/JNEUROSCI.1996-14.2014.
5
ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS.ROCK2是中枢神经系统中轴突退变、神经元死亡和轴突再生的主要调节因子。
Cell Death Dis. 2014 May 15;5(5):e1225. doi: 10.1038/cddis.2014.191.
6
Signaling regulations of neuronal regenerative ability.神经元再生能力的信号调控
Curr Opin Neurobiol. 2014 Aug;27:135-42. doi: 10.1016/j.conb.2014.03.007. Epub 2014 Apr 12.
7
Advances in AAV vector development for gene therapy in the retina.用于视网膜基因治疗的 AAV 载体开发的进展。
Adv Exp Med Biol. 2014;801:687-93. doi: 10.1007/978-1-4614-3209-8_86.
8
Exploiting mTOR signaling: a novel translatable treatment strategy for traumatic optic neuropathy?利用 mTOR 信号通路：外伤性视神经病变有新的可转化治疗策略？
Invest Ophthalmol Vis Sci. 2013 Oct 23;54(10):6903-16. doi: 10.1167/iovs.13-12803.
9
Small-interfering RNAs (siRNAs) as a promising tool for ocular therapy.小干扰RNA（siRNAs）作为一种有前景的眼部治疗工具。
Br J Pharmacol. 2013 Oct;170(4):730-47. doi: 10.1111/bph.12330.
10
RNAi in clinical studies.RNAi 在临床研究中的应用。
Curr Med Chem. 2013;20(14):1801-16. doi: 10.2174/09298673113209990118.