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阿尔茨海默病中的 microRNAs。

MicroRNAs in Alzheimer's disease.

机构信息

Centre de Recherche du CHUQ, Axe Neurosciences, Quebec City, Quebec, Canada G1V4G2.

出版信息

Neurobiol Dis. 2012 May;46(2):285-90. doi: 10.1016/j.nbd.2012.01.003. Epub 2012 Jan 17.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder and is the most common form of dementia in the elderly. Accumulating evidence in AD research suggests that alterations in the microRNA (miRNA) network could contribute to risk for the disease. miRNAs are conserved small non-coding RNAs that control gene expression at the posttranscriptional level and are essential for neuronal function and survival. The results from recent profiling experiments in humans suggest that a number of specific miRNAs are misregulated in disease conditions, several of which have been implicated in the regulation of key genes involved in AD, including APP, BACE1 and MAPT. Moreover, rare disease-specific polymorphisms have been identified in known and putative miRNA target sites located within the 3'untranslated regions (3'UTRs) of APP and BACE1 genes. Here, we review current findings regarding miRNA research in humans and various cellular and animal models to provide a strong basis for future research aimed at understanding the potential contribution of miRNAs to AD pathophysiology.

摘要

阿尔茨海默病(AD)是一种复杂的神经退行性疾病,是老年人中最常见的痴呆症形式。AD 研究中的大量证据表明,miRNA 网络的改变可能导致疾病的发生风险。miRNAs 是保守的小非编码 RNA,可在转录后水平控制基因表达,对神经元功能和存活至关重要。最近在人类中进行的分析实验结果表明,在疾病状态下,许多特定的 miRNAs 被异常调控,其中一些 miRNAs 已被涉及 AD 关键基因的调节,包括 APP、BACE1 和 MAPT。此外,在 APP 和 BACE1 基因的 3'非翻译区(3'UTR)内的已知和假定的 miRNA 靶位点中已经鉴定出罕见的疾病特异性多态性。在这里,我们综述了人类和各种细胞及动物模型中 miRNA 研究的最新发现,为旨在理解 miRNAs 对 AD 病理生理学潜在贡献的未来研究提供了坚实的基础。

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