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microRNAs 作为阿尔茨海默病诊断、预后和治疗靶点的临床工具的作用的深入了解。

Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer's Disease.

机构信息

Department of Life Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Sep 14;25(18):9936. doi: 10.3390/ijms25189936.


DOI:10.3390/ijms25189936
PMID:39337429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11431957/
Abstract

Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders characterized by alterations in the structure and function of the central nervous system. Alzheimer's disease (AD), characterized by impaired memory and cognitive abilities, is the most prevalent type of senile dementia. Loss of synapses, intracellular aggregation of hyperphosphorylated tau protein, and extracellular amyloid-β peptide (Aβ) plaques are the hallmarks of AD. MicroRNAs (miRNAs/miRs) are single-stranded ribonucleic acid (RNA) molecules that bind to the 3' and 5' untranslated regions of target genes to cause post-transcriptional gene silencing. The brain expresses over 70% of all experimentally detected miRNAs, and these miRNAs are crucial for synaptic function and particular signals during memory formation. Increasing evidence suggests that miRNAs play a role in AD pathogenesis and we provide an overview of the role of miRNAs in synapse formation, Aβ synthesis, tau protein accumulation, and brain-derived neurotrophic factor-associated AD pathogenesis. We further summarize and discuss the role of miRNAs as potential therapeutic targets and biomarkers for AD detection and differentiation between early- and late-stage AD, based on recent research. In conclusion, altered expression of miRNAs in the brain and peripheral circulation demonstrates their potential as biomarkers and therapeutic targets in AD.

摘要

神经退行性疾病(NDDs)是一组以中枢神经系统结构和功能改变为特征的多种神经紊乱。阿尔茨海默病(AD)以记忆和认知能力受损为特征,是最常见的老年痴呆症类型。突触丧失、细胞内过度磷酸化 tau 蛋白聚集和细胞外淀粉样-β肽(Aβ)斑块是 AD 的标志。microRNAs(miRNAs/miRs)是单链核糖核酸(RNA)分子,与靶基因的 3'和 5'非翻译区结合,导致转录后基因沉默。大脑表达超过所有实验检测到的 miRNAs 的 70%,这些 miRNAs 对于突触功能和特定的记忆形成信号至关重要。越来越多的证据表明 miRNAs 在 AD 发病机制中发挥作用,我们概述了 miRNAs 在突触形成、Aβ 合成、tau 蛋白积累以及脑源性神经营养因子相关 AD 发病机制中的作用。根据最近的研究,我们进一步总结和讨论了 miRNAs 作为 AD 检测和区分早期和晚期 AD 的潜在治疗靶点和生物标志物的作用。总之,大脑和外周循环中 miRNAs 的表达改变表明它们具有作为 AD 生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/37d2271a8771/ijms-25-09936-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/23738487a99e/ijms-25-09936-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/b1ab9538bd0d/ijms-25-09936-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/37d2271a8771/ijms-25-09936-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/23738487a99e/ijms-25-09936-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/b1ab9538bd0d/ijms-25-09936-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/11431957/37d2271a8771/ijms-25-09936-g003.jpg

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Int J Mol Sci. 2024-9-14

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[10]
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引用本文的文献

[1]
Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer's and Parkinson's Diseases.

Neurol Int. 2025-2-7

本文引用的文献

[1]
MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons.

Neural Regen Res. 2024-12-1

[2]
The roles of long non-coding RNAs in Alzheimer's disease diagnosis, treatment, and their involvement in Alzheimer's disease immune responses.

Noncoding RNA Res. 2024-3-16

[3]
Molecular Mechanism of Alzheimer's Disease.

Int J Mol Sci. 2023-11-28

[4]
Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer's disease.

Pathol Res Pract. 2024-1

[5]
Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases.

Behav Neurol. 2023

[6]
miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

Neurologia (Engl Ed). 2023-9

[7]
The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies.

Int J Mol Sci. 2023-8-17

[8]
Development of microRNA-based therapeutics for central nervous system diseases.

Eur J Pharmacol. 2023-10-5

[9]
Tau and neuroinflammation in Alzheimer's disease: interplay mechanisms and clinical translation.

J Neuroinflammation. 2023-7-14

[10]
Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.

Signal Transduct Target Ther. 2023-6-30

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