文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

靶向 RUNX3-miR-186-3p-DAT-IGF1R 轴作为帕金森病模型中的治疗策略。

Targeting the RUNX3-miR-186-3p-DAT-IGF1R axis as a therapeutic strategy in a Parkinson's disease model.

机构信息

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.

Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.

出版信息

J Transl Med. 2024 Aug 5;22(1):719. doi: 10.1186/s12967-024-05535-7.

DOI:10.1186/s12967-024-05535-7
PMID:39103832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11299274/
Abstract

With the increasing age of the population worldwide, the incidence rate of Parkinson's disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease. In the present study, whole transcriptome sequencing was used to obtain the mRNA and miRNA expression profiles in a PD mouse model, which revealed the pathogenesis of PD. The transcription factor RUNX3 upregulated the miR-186-3p expression in the PD model. Furthermore, the high miR-186-3p expression in PD can be targeted to inhibit the DAT expression, resulting in a decrease in the dopamine content of dopaminergic neurons. Moreover, miR-186-3p can be targeted to inhibit the IGF1R expression and prevent the activation of the IGF1R-P-PI3K-P-AKT pathway, thus increasing the apoptosis of dopaminergic neurons by regulating the cytochrome c-Bax-cleaved caspase-3 pathway. Our research showed that the RUNX3-miR-186-3p-DAT-IGF1R axis plays a key role in the pathogenesis of PD, and miR-186-3p is a potential target for the treatment of PD.

摘要

随着全球人口老龄化，帕金森病（PD）的发病率逐年上升。目前，PD 的治疗策略仅能改善临床症状，尚无有效的治疗策略能减缓疾病的进展。本研究通过全转录组测序获得 PD 小鼠模型中的 mRNA 和 miRNA 表达谱，揭示了 PD 的发病机制。转录因子 RUNX3 上调 PD 模型中的 miR-186-3p 表达。此外，PD 中高表达的 miR-186-3p 可靶向抑制 DAT 表达，导致多巴胺能神经元中多巴胺含量降低。此外，miR-186-3p 可靶向抑制 IGF1R 表达，阻止 IGF1R-P-PI3K-P-AKT 通路的激活，从而通过调节细胞色素 c-Bax-裂解的 caspase-3 通路增加多巴胺能神经元的凋亡。我们的研究表明，RUNX3-miR-186-3p-DAT-IGF1R 轴在 PD 的发病机制中起关键作用，miR-186-3p 是治疗 PD 的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/b4b659461caa/12967_2024_5535_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/77236de507e3/12967_2024_5535_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/00a8aa013bfe/12967_2024_5535_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/70e444f3158a/12967_2024_5535_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/4154305b2925/12967_2024_5535_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/31e3be77654f/12967_2024_5535_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/0bd6edbe130a/12967_2024_5535_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/982319588151/12967_2024_5535_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/682f7a2bdfff/12967_2024_5535_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/090a407e84f6/12967_2024_5535_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/b4b659461caa/12967_2024_5535_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/77236de507e3/12967_2024_5535_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/00a8aa013bfe/12967_2024_5535_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/70e444f3158a/12967_2024_5535_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/4154305b2925/12967_2024_5535_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/31e3be77654f/12967_2024_5535_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/0bd6edbe130a/12967_2024_5535_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/982319588151/12967_2024_5535_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/682f7a2bdfff/12967_2024_5535_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/090a407e84f6/12967_2024_5535_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbd/11299274/b4b659461caa/12967_2024_5535_Fig9_HTML.jpg

相似文献

[1]
Targeting the RUNX3-miR-186-3p-DAT-IGF1R axis as a therapeutic strategy in a Parkinson's disease model.

J Transl Med. 2024-8-5

[2]
Suppression of microRNA-342-3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21-activated kinase 1 in mice with Parkinson's disease.

J Cell Physiol. 2018-10-26

[3]
The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease.

Neurochem Res. 2023-3

[4]
HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 miR-221-3p binding.

Aging (Albany NY). 2020-5-12

[5]
MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1.

Cell Physiol Biochem. 2018

[6]
Regulatory Mechanism of miR-543-3p on GLT-1 in a Mouse Model of Parkinson's Disease.

ACS Chem Neurosci. 2019-2-7

[7]
Overexpression of miR-301a-3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer-1 and runt-related transcription factor 3.

J Cell Biochem. 2018-10-25

[8]
MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian.

Oncotarget. 2017-1-3

[9]
MicroRNA-185 activates PI3K/AKT signalling pathway to alleviate dopaminergic neuron damage via targeting IGF1 in Parkinson's disease.

J Drug Target. 2021-9

[10]
miR-214-3p promotes the pathogenesis of Parkinson's disease by inhibiting autophagy.

Biomed Pharmacother. 2024-2

引用本文的文献

[1]
Dysregulated microRNAs in blood correlate with central nervous system neuropathology of prion disease.

Vet Res. 2025-7-1

本文引用的文献

[1]
Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

Am J Ther.

[2]
The simultaneous presence of demoralization, apathy, and depression has a detrimental impact on both cognitive function and motor symptoms in Parkinson's disease patients.

Front Psychiatry. 2024-2-9

[3]
Types of RNA therapeutics.

Prog Mol Biol Transl Sci. 2024

[4]
Phosphorylation Codes in IRS-1 and IRS-2 Are Associated with the Activation/Inhibition of Insulin Canonical Signaling Pathways.

Curr Issues Mol Biol. 2024-1-9

[5]
The pathogenesis of Parkinson's disease.

Lancet. 2024-1-20

[6]
MiR-184 Mediated the Expression of ZNF865 in Exosome to Promote Procession in the PD Model.

Mol Neurobiol. 2024-6

[7]
Methods of miRNA delivery and possibilities of their application in neuro-oncology.

Noncoding RNA Res. 2023-10-7

[8]
Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3β signaling pathway.

Psychopharmacology (Berl). 2023-9

[9]
Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons.

Elife. 2023-7-6

[10]
Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.

J Neuroinflammation. 2023-5-16

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索