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长链非编码RNA与阿尔茨海默病之间的关联

The Association between Long Non-Coding RNAs and Alzheimer's Disease.

作者信息

Black Carson M, Braden Anneliesse A, Nasim Samia, Tripathi Manish, Xiao Jianfeng, Khan Mohammad Moshahid

机构信息

Departments of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Brain Sci. 2024 Aug 15;14(8):818. doi: 10.3390/brainsci14080818.

Abstract

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease.

摘要

随着人类年龄的增长,神经退行性变会自然发生,但其他致病机制的存在会对大脑产生有害且严重的影响。阿尔茨海默病(AD)是最常见的痴呆形式,就是这些因素的综合体现。尽管已经进行了广泛研究以确定AD的确切病因,但治疗该疾病的方法仍然无效,这表明我们对疾病机制的理解存在重大差距。长链非编码RNA(lncRNA)是一类内源性调节RNA转录本,长度超过200个核苷酸,参与各种调节网络,其失调在几种神经和非神经疾病中都很明显。LncRNA在所有组织中普遍表达,具有广泛的功能,包括控制细胞分化和发育、对环境刺激作出反应以及其他生理过程。由于在异常病理条件下调节改变,一些lncRNA已被确定为神经退行性变恶化的潜在因素。在神经疾病中,lncRNA是用作生物标志物和药理学靶点的主要候选物。AD的性别相关lncRNA表达以性别依赖的方式改变,这表明需要更多地关注这种关系。总体而言,随着商业企业已经在设计和应用RNA疗法,关于lncRNA及其与神经退行性疾病联系的研究正在呈指数级增长。在这篇综述中,我们全面概述了目前关于lncRNA在AD中作用的知识现状,并讨论了lncRNA作为阿尔茨海默病患者潜在治疗靶点和诊断生物标志物的潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff07/11353078/d5f9dc38f14c/brainsci-14-00818-g001.jpg

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