Over 40% of the human genome is composed of retrotransposons, DNA species that hold the potential to replicate via an RNA intermediate and are evolutionarily related to retroviruses. Retrotransposons are most studied for their ability to jump within a genome, which can cause DNA damage and novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal cytoplasmic DNAs, can also be potent activators of the innate immune system. A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders and that such activation causally contributes to neurotoxicity. Here we provide an overview of retrotransposon biology and outline evidence of retrotransposon activation in age-related neurodegenerative disorders, with an emphasis on those involving TAR-DNA binding protein-43 (TDP-43) and tau. Studies to date provide the basis for ongoing clinical trials and hold promise for innovative strategies to ameliorate the adverse effects of retrotransposon dysregulation in neurodegenerative disorders.

中文翻译：

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逆转录转座子和内源性逆转录病毒在年龄依赖性神经退行性疾病中的作用


超过 40% 的人类基因组由逆转录转座子组成，逆转录转座子是具有通过 RNA 中间体进行复制的潜力的 DNA 物种，并且在进化上与逆转录病毒相关。逆转录转座子最受研究的是它们在基因组内跳跃的能力，这可能导致 DNA 损伤和新的插入突变。逆转录转座子编码的产物，包括病毒样蛋白、双链RNA和染色体外细胞质DNA，也可以是先天免疫系统的有效激活剂。越来越多的证据表明，逆转录转座子在与年龄相关的神经退行性疾病中被激活，并且这种激活会导致神经毒性。在这里，我们概述了反转录转座子生物学，并概述了年龄相关神经退行性疾病中反转录转座子激活的证据，重点是涉及 TAR-DNA 结合蛋白 43 (TDP-43) 和 tau 的证据。迄今为止的研究为正在进行的临床试验提供了基础，并为改善神经退行性疾病中逆转录转座子失调的不利影响的创新策略带来了希望。