Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
Trends Genet. 2020 Aug;36(8):610-623. doi: 10.1016/j.tig.2020.05.004. Epub 2020 Jun 1.
The etiology of most neurological disorders is poorly understood and current treatments are largely ineffective. New ideas and concepts are therefore vitally important for future research in this area. This review explores the concept that dysregulation of transposable elements (TEs) contributes to the appearance and pathology of neurodevelopmental and neurodegenerative disorders. Despite TEs making up at least half of the human genome, they are vastly understudied in relation to brain disorders. However, recent advances in sequencing technologies and gene editing approaches are now starting to unravel the pathological role of TEs. Aberrant activation of TEs has been found in many neurological disorders; the resulting pathogenic effects, which include alterations of gene expression, neuroinflammation, and direct neurotoxicity, are starting to be resolved. An increased understanding of the relationship between TEs and pathological processes in the brain improves the potential for novel diagnostics and interventions for brain disorders.
大多数神经紊乱的病因都知之甚少,目前的治疗方法大多无效。因此,新的想法和概念对于该领域未来的研究至关重要。本综述探讨了转座元件 (TEs) 失调导致神经发育和神经退行性疾病出现和病理的概念。尽管 TEs 至少占人类基因组的一半,但与大脑疾病相比,它们的研究还远远不够。然而,测序技术和基因编辑方法的最新进展现在开始揭示 TEs 的病理作用。TE 的异常激活已在许多神经紊乱中发现;由此产生的致病作用,包括基因表达改变、神经炎症和直接神经毒性,开始得到解决。对 TEs 与大脑病理过程之间关系的深入了解提高了针对大脑疾病的新型诊断和干预措施的潜力。