Department of Physiology, Neuroscience and Behavioral Sciences, St. George's University School of Medicine, Grenada, West Indies.
Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Int J Mol Sci. 2021 Nov 13;22(22):12280. doi: 10.3390/ijms222212280.
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.
表观遗传机制，包括 DNA 甲基化、组蛋白蛋白质的各种翻译后修饰（乙酰化、磷酸化、甲基化、泛素化、SUMO 化、丝氨酸化、多巴胺化）、染色质重塑酶和长非编码 RNA，是基因转录中活性依赖性变化的强大调节因子。在大脑中，这些表观遗传修饰中的许多都广泛涉及突触可塑性和记忆形成。在衰老的大脑中已经报道了表观遗传机制的失调，并且与整个生命周期中的记忆衰退有关或有助于记忆衰退。此外，在神经退行性疾病中，包括阿尔茨海默病，已经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失调，并导致年龄增长和阿尔茨海默病中的记忆丧失。总的来说，这里回顾的证据强烈支持多种表观遗传机制在大脑中的记忆形成、衰老和神经退行性变中的作用。
