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转录组分析鉴定了新型潜在生物标志物,并强调了在小鼠朊病毒病早期阶段与纤毛相关的生物学过程。

Transcriptomic analysis identifies novel potential biomarkers and highlights cilium-related biological processes in the early stages of prion disease in mice.

机构信息

Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Republic of Korea.

Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Republic of Korea.

出版信息

Prion. 2022 Dec;16(1):84-90. doi: 10.1080/19336896.2022.2095186.

DOI:10.1080/19336896.2022.2095186
PMID:35786398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9255203/
Abstract

Prion diseases are fatal and irreversible neurodegenerative diseases induced by the pathogenic form of the prion protein (PrP), which is converted from the benign form of the prion protein (PrP). These diseases are characterized by an extended asymptomatic incubation period accompanied by continuous conversion of PrP to PrP. However, to date, the mechanism governing the conversion to PrP in the initial stages of prion disease has not been fully elucidated. We collected transcriptome data from the hippocampus of wild-type mice and prion-infected mice at 8 weeks post injection from the Gene Expression Omnibus and analysed differentially expressed genes and related signalling biological process using bioinformatic tools. We identified a total of 36 differentially expressed genes, including 22 upregulated genes and 14 downregulated genes. In addition, we identified that the cilium-related biological process was enriched in the early stages of prion disease. Furthermore, up- and down-regulated genes were associated with cilium-related cellular components and synapse-related cellular components, respectively. To the best of our knowledge, our study was the first to observe the upregulation of cilium-related genes in the early stages of prion disease.

摘要

朊病毒病是由朊病毒蛋白(PrP)的致病性形式引起的致命且不可逆转的神经退行性疾病,该蛋白由朊病毒蛋白(PrP)的良性形式转化而来。这些疾病的特征是潜伏期长且无症状,同时伴随着 PrP 向 PrP 的持续转化。然而,迄今为止,朊病毒病初期 PrP 转化的机制尚未完全阐明。我们从基因表达综合数据库中收集了野生型和感染朊病毒的小鼠在注射后 8 周的海马转录组数据,并使用生物信息学工具分析差异表达基因和相关信号生物学过程。我们共鉴定出 36 个差异表达基因,包括 22 个上调基因和 14 个下调基因。此外,我们还发现纤毛相关的生物学过程在朊病毒病的早期阶段富集。此外,上调和下调的基因分别与纤毛相关的细胞成分和突触相关的细胞成分相关。据我们所知,我们的研究首次观察到朊病毒病早期纤毛相关基因的上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e6/9255203/3cc7beefe81f/KPRN_A_2095186_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e6/9255203/8eeb86d7cc4e/KPRN_A_2095186_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e6/9255203/3cc7beefe81f/KPRN_A_2095186_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e6/9255203/8eeb86d7cc4e/KPRN_A_2095186_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e6/9255203/3cc7beefe81f/KPRN_A_2095186_F0002_OC.jpg

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本文引用的文献

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In-depth examination of PrP in Holstein cattle carrying the E211K somatic mutation of the bovine prion protein gene (PRNP).对携带牛朊病毒蛋白基因(PRNP)E211K体细胞突变的荷斯坦奶牛中的朊病毒蛋白(PrP)进行深入研究。
Transbound Emerg Dis. 2022 Jul;69(4):e356-e361. doi: 10.1111/tbed.14309. Epub 2021 Sep 12.
2
Altered expression of glymphatic system-related proteins in prion diseases: Implications for the role of the glymphatic system in prion diseases.朊病毒疾病中类淋巴系统相关蛋白的表达改变:类淋巴系统在朊病毒疾病中的作用启示
Cell Mol Immunol. 2021 Sep;18(9):2281-2283. doi: 10.1038/s41423-021-00747-z. Epub 2021 Aug 6.
3
Large-scale lipidomic profiling identifies novel potential biomarkers for prion diseases and highlights lipid raft-related pathways.
大规模脂质组学分析鉴定出朊病毒病的新型潜在生物标志物,并突出了脂筏相关途径。
Vet Res. 2021 Jul 21;52(1):105. doi: 10.1186/s13567-021-00975-1.
4
Absence of proteinase K-resistant PrP in Korean Holstein cattle carrying potential bovine spongiform encephalopathy-related E211K somatic mutation.携带潜在的与牛海绵状脑病相关的E211K体细胞突变的韩国荷斯坦奶牛中不存在抗蛋白酶K的朊蛋白。
Transbound Emerg Dis. 2022 Mar;69(2):805-812. doi: 10.1111/tbed.14053. Epub 2021 Mar 31.
5
Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses.朊病毒诱导的光感受器退化始于错误折叠的朊病毒蛋白在视锥细胞的两个不同部位积累:纤毛和带状突触。
Acta Neuropathol Commun. 2021 Jan 29;9(1):17. doi: 10.1186/s40478-021-01120-x.
6
Genome-wide transcriptomics identifies an early preclinical signature of prion infection.全基因组转录组学鉴定出朊病毒感染的早期临床前特征。
PLoS Pathog. 2020 Jun 29;16(6):e1008653. doi: 10.1371/journal.ppat.1008653. eCollection 2020 Jun.
7
RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection.RNA-seq 和网络分析揭示朊病毒感染过程中独特的神经胶质基因表达特征。
Mol Brain. 2020 May 7;13(1):71. doi: 10.1186/s13041-020-00610-8.
8
The role of motile cilia in the development and physiology of the nervous system.纤毛在神经系统发育和生理学中的作用。
Philos Trans R Soc Lond B Biol Sci. 2020 Feb 17;375(1792):20190156. doi: 10.1098/rstb.2019.0156. Epub 2019 Dec 30.
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Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation.克雅氏病:全球发病率、患病率、传染性和潜伏期的系统综述。
Lancet Infect Dis. 2020 Jan;20(1):e2-e10. doi: 10.1016/S1473-3099(19)30615-2.
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