Stanley Center for Psychiatric Research, Broad Institute of MIT & Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Future Med Chem. 2013 Sep;5(13):1491-508. doi: 10.4155/fmc.13.141.
Increasing evidence supports a role for epigenetic involvement in some of the neurobiological alterations observed in neurodegenerative and psychiatric disorders including schizophrenia. In particular, there is mounting evidence implicating dysfunction in acetylation status, a chromatin modification mediated in part by HDACs, as a possible contributing factor to certain facets of this debilitating disease. Additional data support the notion that small molecule inhibition of HDACs may provide therapeutic alternatives to treating many of the symptoms associated with schizophrenia, particularly cognitive deficits. However, the development of highly potent and selective inhibitors of the individual HDAC isoforms will be necessary to delineate the associated biological effects and test the feasibility of such an approach for this complex and chronically treated disease. Here, we summarize current evidence for the role of HDAC isoforms in schizophrenia and highlight the state of the art in developing selective inhibitors of these isoforms as a potential treatment for schizophrenia.
越来越多的证据表明，表观遗传参与了一些神经退行性和精神疾病（包括精神分裂症）中观察到的神经生物学改变。特别是，越来越多的证据表明，乙酰化状态的功能障碍，部分由 HDAC 介导的染色质修饰，可能是导致这种使人衰弱的疾病某些方面的一个可能的促成因素。更多的数据支持这样一种观点，即小分子抑制 HDAC 可能为治疗许多与精神分裂症相关的症状，特别是认知缺陷，提供治疗选择。然而，开发个体 HDAC 同工型的高活性和选择性抑制剂对于描绘相关的生物学效应以及测试这种方法治疗这种复杂和慢性疾病的可行性是必要的。在这里，我们总结了 HDAC 同工型在精神分裂症中的作用的现有证据，并强调了开发这些同工型的选择性抑制剂作为精神分裂症潜在治疗方法的最新进展。
