Transposable elements as new players in neurodegenerative diseases,FEBS Letters

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Transposable elements as new players in neurodegenerative diseases
FEBS Letters ( IF 3.0 ) Pub Date : 2021-10-09 , DOI: 10.1002/1873-3468.14205
Camille Ravel-Godreuil ₁ , Rania Znaidi ₁ , Tom Bonnifet ₁ , Rajiv L Joshi ₁ , Julia Fuchs ₁

Affiliation

Neurodegenerative diseases (NDs), including the most prevalent Alzheimer’s disease and Parkinson disease, share common pathological features. Despite decades of gene-centric approaches, the molecular mechanisms underlying these diseases remain widely elusive. In recent years, transposable elements (TEs), long considered ‘junk’ DNA, have gained growing interest as pathogenic players in NDs. Age is the major risk factor for most NDs, and several repressive mechanisms of TEs, such as heterochromatinization, fail with age. Indeed, heterochromatin relaxation leading to TE derepression has been reported in various models of neurodegeneration and NDs. There is also evidence that certain pathogenic proteins involved in NDs (e.g., tau, TDP-43) may control the expression of TEs. The deleterious consequences of TE activation are not well known but they could include DNA damage and genomic instability, altered host gene expression, and/or neuroinflammation, which are common hallmarks of neurodegeneration and aging. TEs might thus represent an overlooked pathogenic culprit for both brain aging and neurodegeneration. Certain pathological effects of TEs might be prevented by inhibiting their activity, pointing to TEs as novel targets for neuroprotection.

中文翻译：

转座因子作为神经退行性疾病的新参与者

神经退行性疾病 (NDs)，包括最普遍的阿尔茨海默病和帕金森病，具有共同的病理特征。尽管几十年来以基因为中心的方法，这些疾病的分子机制仍然广泛难以捉摸。近年来，长期以来被认为是“垃圾”DNA 的转座因子 (TE) 作为 ND 中的致病因素越来越受到关注。年龄是大多数 ND 的主要危险因素，并且 TE 的几种抑制机制，如异染色质化，会随着年龄的增长而失效。事实上，已经在各种神经变性和 ND 模型中报道了异染色质松弛导致 TE 去抑制。也有证据表明某些致病蛋白与 NDs 相关（例如., tau, TDP-43) 可以控制 TE 的表达。TE 激活的有害后果尚不清楚，但它们可能包括 DNA 损伤和基因组不稳定性、宿主基因表达改变和/或神经炎症，这些都是神经变性和衰老的常见标志。因此，TE 可能是导致大脑衰老和神经变性的被忽视的致病罪魁祸首。TEs 的某些病理作用可以通过抑制它们的活性来预防，这表明 TEs 是神经保护的新靶点。

更新日期：2021-11-22

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