Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease.
Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease.
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DOI：
10.1038/s42003-021-01868-x
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发表时间：
2021-03-25
影响因子：
5.9
通讯作者：
Hill AF
中科院分区：
文献类型：
--
作者：
Cheng L;Quek C;Li X;Bellingham SA;Ellett LJ;Shambrook M;Zafar S;Zerr I;Lawson VA;Hill AF
Prion疾病的特点是临床前潜伏期较长，在此期间Prion在大脑中活跃繁殖并导致神经退化。在临床前阶段，我们假设在感染Prion后，会发生转录变化，从而导致早期神经退化。对临床前和临床形式的小鼠Pron病的miRNAs的纵向分析表明，在疾病进展过程中，受影响丘脑区域和血清中miRNAs的表达发生了动态变化。收集每个时间点的血清样本，分离细胞外小泡(EV)，并用于识别反映大脑病理的血液生物标记物。在人类散发性克雅氏病患者的临床标本中验证了差异表达的EV miRNAs，与对照组(n = 20)相比，分子亚型位于第129位密码子的蛋氨酸-蛋氨酸(MM，n = 14)或Valine-Valine(Vv，n = 12)。与Pron感染相关的EV miRNA生物标志物在第二个独立验证队列(n = 26)中预测SCJD的AUC值为0.800(灵敏度为85%，特异度为66.7%)，MM或VV亚型的对照患者。这项研究发现了临床上相关的miRNAs，这些miRNAs有助于诊断发展，以检测与Pron相关的疾病，并有助于治疗发展，以抑制Pron的传染性。程等人散发性克雅氏病患者的临床样本中存在差异表达的胞外囊泡miRNAs。这项研究确定了可用于检测普恩病毒相关疾病的生物标志物，为抑制普恩病毒感染性的药物开发提供了见解。
Prion diseases are distinguished by long pre-clinical incubation periods during which prions actively propagate in the brain and cause neurodegeneration. In the pre-clinical stage, we hypothesize that upon prion infection, transcriptional changes occur that can lead to early neurodegeneration. A longitudinal analysis of miRNAs in pre-clinical and clinical forms of murine prion disease demonstrated dynamic expression changes during disease progression in the affected thalamus region and serum. Serum samples at each timepoint were collected whereby extracellular vesicles (EVs) were isolated and used to identify blood-based biomarkers reflective of pathology in the brain. Differentially expressed EV miRNAs were validated in human clinical samples from patients with human sporadic Creutzfeldt-Jakob disease (sCJD), with the molecular subtype at codon 129 either methionine-methionine (MM, n = 14) or valine-valine (VV, n = 12) compared to controls (n = 20). EV miRNA biomarkers associated with prion infection predicted sCJD with an AUC of 0.800 (85% sensitivity and 66.7% specificity) in a second independent validation cohort (n = 26) of sCJD and control patients with MM or VV subtype. This study discovered clinically relevant miRNAs that benefit diagnostic development to detect prion-related diseases and therapeutic development to inhibit prion infectivity. Cheng et al. present differentially expressed extracellular vesicle miRNAs in human clinical samples from patients who suffer from sporadic Creutzfeldt-Jakob disease. This study identifies biomarkers that can be used to detect prion-related diseases, providing insights into drug development for inhibiting prion infectivity.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
16.6
作者：
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通讯作者：
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影响因子：
7.3
作者：
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通讯作者：
Stanimirovic DB
影响因子：
29
作者：
Bizzi, Alberto;Pascuzzo, Riccardo;Gambetti, Pierluigi
通讯作者：
Gambetti, Pierluigi
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影响因子：
13.2
作者：
Gao, Chen;Wei, Jing;Zhang, Bao-Yun;Shi, Qiang;Chen, Cao;Wang, Jing;Shi, Qi;Dong, Xiao-Ping
通讯作者：
Dong, Xiao-Ping