MicroRNA 是小型非编码 RNA 进化保守分子。它们调节细胞过程，包括 RNA 沉默、翻译后基因表达和神经变性。 MicroRNA 与癌症、阿尔茨海默病 (AD) 等人类疾病有关。有趣的是，AD 患者的脑脊液 (CSF) 和血液中许多 RNA 的表达发生了改变，这可能作为潜在的外周生物标志物。我们实验室的深入研究表明，microRNA-455-3P (miR-455-3p) 是 AD 潜在生物标志物和治疗靶点的有力候选者。 miR-455-3p 直接靶向与 AD 发病机制有关的几个基因。我们几年的实验室研究表明，miR-455-3p 调节与 AD 相关的重要生理过程，例如淀粉样前体蛋白 (APP) 的加工、TGF-β 信号传导、氧化应激的调节、线粒体生物发生和突触损害。轻度认知障碍受试者和 AD 患者中 miR-455-3p 的表达表明其参与 AD 进展。最近，我们的实验室培育了 miR-455-3p 转基因小鼠和基因敲除小鼠。有趣的是，与年龄匹配的野生型小鼠相比，miR-455-3p转基因小鼠表现出优异的认知学习能力、改善的记忆力和延长的寿命，而miR-455-3-p敲除小鼠则表现出认知能力下降和寿命缩短。来自小鼠模型的信息进一步证明了 miR-455-3p 对树突生长、突触发生和线粒体生物发生在预防 AD 发病和进展方面的有利影响。 miR-455-3p 在死后 AD 大脑、B 淋巴细胞和成纤维细胞中的存在表明其被鉴定为生物标志物。我们假设 miR-455-3p 可能是 AD 的外周生物标志物和治疗靶点。版权所有 © 2024 Elsevier B.V. 保留所有权利。

MicroRNAs are small non-coding RNAs evolutionary conserved molecules. They regulate cellular processes, including RNA silencing, post-translational gene expression and neurodegeneration. MicroRNAs are involved with human diseases such as cancer, Alzheimer's disease (AD) and others. Interestingly, cerebrospinal fluids (CSF) and the blood of AD patients have altered expressions of many RNAs, which may serve as potential peripheral biomarkers. The intensive investigation from our lab revealed that microRNA-455-3P (miR-455-3p) is a strong candidate as a potential biomarker and therapeutic target for AD. Several genes implicated in the pathogenesis of AD are directly targeted by miR-455-3p. Several years of our lab research revealed that miR-455-3p regulates important physiological processes associated with AD, such as the processing of the amyloid precursor protein (APP), TGF-β signaling, the regulation of oxidative stress, mitochondrial biogenesis, and synaptic damages. The expression of miR-455-3p in mild cognitive impaired subjects and AD patients pointed out its involvement in AD progression. Recently, our lab generated both transgenic and knockout mice for miR-455-3p. Interestingly miR-455-3p transgenic mice showed superior cognitive learning, improved memory and extended lifespan compared to age matched wild-type mice, whereas miR-455-3-p knockout mice showed cognitive decline and reduced lifespan. Information derived from mouse models further demonstrated the advantageous impact of miR-455-3p on dendritic growth, synaptogenesis, and mitochondrial biogenesis in preventing the onset and progression of AD. The identification of miR-455-3p as a biomarker was suggested by its presence in postmortem AD brains, B-lymphocytes, and fibroblasts. Our hypothesis that miR-455-3p could be a peripheral biomarker and therapeutic target for AD.Copyright © 2024 Elsevier B.V. All rights reserved.