Ramirez-Gomez Jaime, Dalal Sarthak, Devara Davin, Sharma Bhupender, Rodarte Daniela, Kumar Subodh
Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
L. Frederick Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA.
J Alzheimers Dis. 2025 Mar;104(1):14-31. doi: 10.1177/13872877241313397. Epub 2025 Feb 2.
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by memory and physical impairment in aged individuals. microRNAs (miRNAs) are small, single-stranded noncoding RNAs that induce translational repression by binding to the 3' UTR of a target mRNA. miRNAs play a crucial role in neurological activity by mediating cellular proliferation, synaptic plasticity, apoptosis and more. Ongoing research in patents and clinical trials have called attention to promising miRNAs as biomarkers and therapeutics in AD. Recent research has shown that miRNAs are aberrantly expressed in AD brain, blood, cerebrospinal fluid and serum. Attenuated miRNA expressions have diagnostic potential in AD by interacting with amyloid-β synthesis, phosphorylated tau, and neurofibrillary tangles. In this study, miRNA-29a, miRNA-125b, miRNA-34a, miRNA-146a, and miRNA-155 have shown promise as potential biomarker candidates for AD. Improving cognitive symptoms can be traced to restoring the endogenous miRNA activity by synthesizing miRNA mimics and miRNA antisense oligonucleotides. miRNA-483-5p, miRNA-188-5p, miRNA-219, miRNA135a/5p, miRNA-23/23b-3p, miRNA-124, and miRNA-455-3p are growing therapeutics for AD. However, miRNA-based therapeutics struggle outside of preclinical testing. miRNA-107, miRNA-206, miRNA-30/7, and miRNA-142-3p face bottlenecks in clinical trials due to a lack of experimental design, transparency and volunteer size. Patenting recent miRNA-based developments demonstrates the commitment in identifying a new biomarker and/or therapeutic for AD.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，其特征是老年个体出现记忆和身体功能障碍。微小RNA（miRNA）是小的单链非编码RNA，通过与靶mRNA的3'非翻译区（UTR）结合来诱导翻译抑制。miRNA通过介导细胞增殖、突触可塑性、细胞凋亡等在神经活动中发挥关键作用。专利和临床试验中的 ongoing 研究已将有前景的miRNA作为AD的生物标志物和治疗方法引起关注。最近的研究表明，miRNA在AD大脑、血液、脑脊液和血清中异常表达。miRNA表达减弱通过与淀粉样β蛋白合成、磷酸化tau蛋白和神经原纤维缠结相互作用，在AD中具有诊断潜力。在本研究中，miRNA-29a、miRNA-125b、miRNA-34a、miRNA-146a和miRNA-155已显示出作为AD潜在生物标志物候选物的前景。改善认知症状可追溯到通过合成miRNA模拟物和miRNA反义寡核苷酸来恢复内源性miRNA活性。miRNA-483-5p、miRNA-188-5p、miRNA-219、miRNA135a/5p、miRNA-23/23b-3p、miRNA-124和miRNA-455-3p正在成为AD的治疗方法。然而，基于miRNA的治疗方法在临床前测试之外面临困难。miRNA-107、miRNA-206、miRNA-30/7和miRNA-142-3p由于缺乏实验设计、透明度和志愿者规模，在临床试验中面临瓶颈。对最近基于miRNA的进展进行专利申请表明了在确定AD的新生物标志物和/或治疗方法方面的努力。 （注：原文中“ongoing”未准确翻译，可结合语境理解为“正在进行的” ）
