核膜侵蚀引起的内源性逆转录病毒的复活是神经元衰老的基础
Hui Zhang1, Jiaming Li2, Yang Yu3
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell reports
|June 1, 2023
概括
老龄化灵长类动物的额叶显示出分子变化,如DNA损伤和炎症. 这些可以通过药物阿巴卡维尔逆转,为神经认知衰退提供潜在的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 老年学是指老年学的学科.
- 分子生物学分子生物学
背景情况:
- 灵长类动物的额叶 (FL) 经历了与年龄有关的神经认知衰退,但根本的分子机制尚未完全理解.
- 识别这些机制对于开发针对认知衰老的干预措施至关重要.
研究的目的:
- 为了全面描述灵长类动物额叶衰老的分子场景.
- 阐明FL衰老中关键的分子事件和途径.
- 确定潜在的治疗目标,以减轻与年龄相关的衰退.
主要方法:
- 对生理上老化的非人类灵长类动物 (NHPs) 进行多维分子分析,包括批量和单核转录组,定量蛋白质组和DNA甲基组.
- 联合分析将多学科数据与神经病理学发现整合起来.
- 使用人类胚胎干细胞衍生的神经元进行体外研究,以验证分子发现.
- 在老年小鼠体内研究以评估治疗疗效.
主要成果:
- 灵长类动物FL的衰老的特征是核膜和异色染色体侵蚀,内源逆转录病毒 (ERV) 的重新激活,cGAS信号的激活,以及神经元转移后的神经元的细胞衰老.
- 认定B型层膜的损失是老化神经元中ERV复活的起始事件.
- 药物阿巴卡维尔在减轻与衰老相关的分子和细胞变化方面表现出有效性,在体外和体内.
结论:
- 灵长类动物额叶的衰老涉及特定的分子途径,包括核完整性丧失,ERV激活和炎症.
- 阿巴卡维尔作为一种治疗药物,有望抵消神经元中关键的衰老过程,可能改善神经认知衰退.
更多相关视频
相关概念视频
Non-LTR Retrotransposons
11.6K
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...
11.6K
Mechanisms of Retrovirus-induced Cancers
5.2K
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...
5.2K
LTR Retrotransposons
17.6K
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...
17.6K
Retroviruses
12.6K
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’...
12.6K
Retrovirus Life Cycles
46.3K
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...
46.3K
The Nucleolus
8.9K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.9K


