Unique functional roles for class I and class II histone deacetylases in central nervous system development and function.
Unique functional roles for class I and class II histone deacetylases in central nervous system development and function.
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DOI：
10.1016/j.ijdevneu.2013.02.005
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Monteggia LM
中科院分区：
文献类型：
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作者：
Morris MJ;Monteggia LM
组蛋白脱乙酰酶（HDAC）家族酶的非特异性药理学抑制在各种不同的情况下（包括癌症、认知功能和神经变性）具有很大的有益效果。这篇综述将讨论个体HDAC亚型在发育和成人脑功能中的作用。重要的是，I类和II类HDAC表现出不同的细胞和亚细胞表达模式，并利用不同的信号传导途径来影响其底物。此外，在大脑中操纵个体HDAC后出现可分离的表型结果。迄今为止，已经证明难以开发能够靶向个体HDAC的药理学抑制剂，这是必须克服的障碍，以解锁在中枢神经系统中操纵内源性HDAC同种型的实质性临床前景。
Non-specific pharmacological inhibition of the histone deacetylase (HDAC) family of enzymes has largely beneficial effects in a variety of diverse contexts including cancer, cognitive function, and neurodegeneration. This review will discuss the role of individual HDAC isoforms in brain function during development and in the adult. Importantly class I and class II HDACs exhibit distinct cellular and subcellular expression patterns and utilize different signaling pathways to influence their substrates. Moreover, dissociable phenotypic outcomes emerge following manipulation of individual HDACs in the brain. To date, pharmacological inhibitors capable of targeting individual HDACs have proven difficult to develop, an obstacle that must be overcome to unlock the substantial clinical promise of manipulating endogenous HDAC isoforms in the central nervous system.