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可转座元件:神经退行性疾病治疗的新靶点

Transposable Elements: Emerging Therapeutic Targets in Neurodegenerative Diseases.

机构信息

Department of Pharmacology, Bhanuben Nanavati College of Pharmacy, SVKM's DrVile Parle (W), Mumbai, India.

Department of Pharmaceutical Chemistry, SVKM's Dr, Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.

出版信息

Neurotox Res. 2024 Jan 25;42(1):9. doi: 10.1007/s12640-024-00688-1.

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure. While several genetic and environmental factors have been implicated in the pathogenesis of these disorders, emerging evidence suggests that transposable elements (TEs), once considered "junk DNA," play a significant role in their development and progression. TEs are mobile genetic elements capable of moving within the genome, and their dysregulation has been associated with genomic instability, altered gene expression, and neuroinflammation. This review provides an overview of TEs, including long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and endogenous retroviruses (ERVs), mechanisms of repression and derepression, and their potential impact on neurodegeneration. The evidence linking TEs to AD, PD, and ALS by shedding light on the complex interactions between TEs and neurodegeneration has been discussed. Furthermore, the therapeutic potential of targeting TEs in neurodegenerative diseases has been explored. Understanding the role of TEs in neurodegeneration holds promise for developing novel therapeutic strategies aimed at mitigating disease progression and preserving neuronal health.

摘要

神经退行性疾病,如阿尔茨海默病(AD)、帕金森病(PD)和肌萎缩侧索硬化症(ALS),其特征是神经元功能和结构的进行性丧失。虽然有几个遗传和环境因素与这些疾病的发病机制有关,但新出现的证据表明,转座元件(TEs),曾经被认为是“垃圾 DNA”,在它们的发展和进展中起着重要作用。TEs 是能够在基因组内移动的可移动遗传元件,其失调与基因组不稳定性、基因表达改变和神经炎症有关。

这篇综述概述了 TEs,包括长散布核元件(LINEs)、短散布核元件(SINEs)和内源性逆转录病毒(ERVs),包括抑制和去抑制的机制,以及它们对神经退行性变的潜在影响。通过阐明 TEs 与 AD、PD 和 ALS 之间的复杂相互作用,讨论了将 TEs 与这些疾病联系起来的证据。此外,还探讨了针对 TEs 在神经退行性疾病中的治疗潜力。

了解 TEs 在神经退行性变中的作用,有望为开发新的治疗策略提供前景,旨在减轻疾病进展和保护神经元健康。

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