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神经紊乱的表观遗传学探索、鉴定方法和治疗途径。

Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.

机构信息

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Int J Mol Sci. 2024 Oct 30;25(21):11658. doi: 10.3390/ijms252111658.

Abstract

Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales-ranging from low to high-with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches.

摘要

神经退行性疾病是全球主要的健康关注点,尤其是在老龄化社会中。对脑表观基因组的探索,其中包括多种形式的 DNA 甲基化和组蛋白共价修饰,为衰老和神经退行性疾病的机制提供了新的、意想不到的视角。最初,人们认为大脑中的染色质缺陷是与罕见遗传综合征相关的早期发育过程中的静态异常。然而,现在很明显,突变和表观遗传机制的失调在更广泛的范围内扩展,包括成人发病的神经退行性疾病。因此,开发能够增强表观遗传学研究的方法至关重要。已经创建了几种方法来研究在一系列尺度上的表观遗传学变化——从低到高——特别侧重于检测 DNA 甲基化和组蛋白修饰。本文探讨了神经表观遗传学的新兴领域,强调了它在增强我们对神经退行性疾病的机械理解以及阐明用于检测表观基因组修饰的主要技术方面的作用。此外,我们还思考了这些进展对塑造未来治疗方法的潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3185/11546397/f08d1ff171d7/ijms-25-11658-g001.jpg

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