Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease.
Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease.
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DOI：
10.3390/ijms222212280
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发表时间：
2021-11-13
影响因子：
5.6
通讯作者：
Jarome TJ
中科院分区：
文献类型：
--
作者：
Maity S;Farrell K;Navabpour S;Narayanan SN;Jarome TJ
表观遗传机制，包括DNA甲基化，各种组蛋白翻译后修饰（乙酰化，磷酸化，甲基化，泛素化，sumo化，5 -羟色胺化，多巴胺化），染色质重塑酶和长链非编码rna，是基因转录活性依赖性变化的强大调节因子。在大脑中，许多这些表观遗传修饰已广泛涉及突触可塑性和记忆形成。据报道，在老年大脑中，表观遗传机制的失调与整个生命周期的记忆衰退有关或有所贡献。此外，在包括阿尔茨海默病在内的神经退行性疾病中也报道了表观基因组的改变。在这里，我们回顾了不同类型的表观遗传修饰及其在活动和学习依赖性突触可塑性中的作用。然后，我们讨论了这些机制如何在整个生命周期中变得失调，并随着年龄的增长和阿尔茨海默病而导致记忆丧失。总的来说，本文综述的证据有力地支持了多种表观遗传机制在大脑记忆形成、衰老和神经退行性变中的作用。
Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer’s disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer’s disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain.
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