Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nat Rev Neurosci. 2013 Feb;14(2):97-111. doi: 10.1038/nrn3427. Epub 2013 Jan 17.
Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.
长时程记忆需要特定的基因表达程序,这些程序部分是由表观遗传机制调控的。在认知过程中鉴定出的表观遗传修饰中,组蛋白乙酰化引起了相当大的兴趣。尽管组蛋白乙酰化的增加一直被证明有利于学习和记忆,但在神经发育障碍、神经退行性变和衰老中认知障碍的因果关系中,组蛋白乙酰化的缺乏一直被认为是认知障碍的原因。由于组蛋白去乙酰化酶抑制剂可以使组蛋白乙酰化和认知功能在药理学上恢复,这种表观遗传修饰可能构成染色质上的分子记忆辅助,并且可以作为治疗认知脆弱性的新模板。