衰老和神经退行性变中的重复元件。
Repetitive elements in aging and neurodegeneration.
机构信息
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Neuroscience Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Neuroscience Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Trends Genet. 2023 May;39(5):381-400. doi: 10.1016/j.tig.2023.02.008. Epub 2023 Mar 17.
Repetitive elements (REs), such as transposable elements (TEs) and satellites, comprise much of the genome. Here, we review how TEs and (peri)centromeric satellite DNA may contribute to aging and neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Alterations in RE expression, retrotransposition, and chromatin microenvironment may shorten lifespan, elicit neurodegeneration, and impair memory and movement. REs may cause these phenotypes via DNA damage, protein sequestration, insertional mutagenesis, and inflammation. We discuss several TE families, including gypsy, HERV-K, and HERV-W, and how TEs interact with various factors, including transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and the siRNA and piwi-interacting (pi)RNA systems. Studies of TEs in neurodegeneration have focused on Drosophila and, thus, further examination in mammals is needed. We suggest that therapeutic silencing of REs could help mitigate neurodegenerative disorders.
重复元件（REs），如转座元件（TEs）和卫星，构成了基因组的很大一部分。在这里，我们回顾了 TEs 和（peri）着丝粒卫星 DNA 如何可能导致衰老和神经退行性疾病，包括肌萎缩侧索硬化症（ALS）。RE 表达、逆转录转座和染色质微环境的改变可能会缩短寿命、引发神经退行性变，并损害记忆和运动能力。RE 可能通过 DNA 损伤、蛋白质隔离、插入诱变和炎症引起这些表型。我们讨论了几个 TE 家族，包括 gypsy、HERV-K 和 HERV-W，以及 TEs 如何与各种因素相互作用，包括反式激活反应（TAR）DNA 结合蛋白 43kDa（TDP-43）和 siRNA 和 piwi 相互作用（pi）RNA 系统。神经退行性疾病中的 TEs 研究主要集中在果蝇上，因此需要在哺乳动物中进一步研究。我们建议，RE 的治疗性沉默可能有助于减轻神经退行性疾病。
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