对内源性逆转录病毒-K转录在肌缩侧面硬化症中的新见解
Laura Moreno-Martinez1,2,3,4, Sofía Macías-Redondo5, Mark Strunk5
1Laboratory of Genetics and Biochemistry (LAGENBIO), Faculty of Veterinary, University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
International journal of molecular sciences
|February 10, 2024
概括
人体内源逆转录病毒 (HERVs) 与肌缩性侧面硬化症 (ALS) 有关. 特定的HERVK副本,而不是全球表达,显示ALS大脑中的改变模式,表明潜在的诊断价值.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 肌缩侧面硬化症 (ALS) 与逆转录酶活性和人体内源逆转录病毒 (HERVs) 表达的增加有关.
- 特定的HERV-K (HERVK) 副本在ALS病原和潜在的诊断标记物的作用仍在调查中.
研究的目的:
- 为了确认ALS大脑中的HERVK过度表达.
- 评估HERVK作为ALS的诊断标志物.
- 探索在ALS中HERVK表达和神经炎症之间的相互作用.
主要方法:
- 量化PCR (qPCR) 用于分析HERVK表达在外周血液单核细胞 (PBMC) 和ALS患者和对照者的死后脑样本.
- 量化了特定的HERVK位点和炎症标志物 (NLRP3,TNFA,IL6,GZMB) 的表达水平.
- 进行了统计分析,以比较患者和对照组之间的表达模式.
主要成果:
- 与对照组相比,在PBMC或ALS患者的大脑样本中没有发现显著的全球HERVK过度表达.
- 特定的HERVK拷贝在ALS大脑中表现出改变的表达模式,特别是在脑干中.
- 两个HERVK拷贝 (Chr3-3和Chr3-5) 在ALS患者的大脑干中表达明显不同;NLRP3水平增加,而TNFA,IL6和GZMB略有下降.
结论:
- 全球HERVK过度表达不是ALS的标志,但在ALS大脑中发生了特定的HERVK副本改变.
- 选择的HERVK拷贝可能在ALS病变发生过程中发挥作用,并可能对患者分层有价值.
- 需要进一步的研究来阐明特定的HERVK拷贝在ALS中的确切作用以及它们与神经炎症的关系.
相关概念视频
Non-LTR Retrotransposons
11.5K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K
Retroviruses
12.3K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.3K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Retrovirus Life Cycles
46.0K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.0K
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K
LTR Retrotransposons
17.5K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
17.5K


