Alteration of epigenetic program to recover memory and alleviate neurodegeneration: Prospects of multi-target molecules
Alteration of epigenetic program to recover memory and alleviate neurodegeneration: Prospects of multi-target molecules
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改变表观遗传程序以恢复记忆和减轻神经退行性变：多靶点分子的前景
DOI：
10.1039/c4bm00068d
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
and H. Sugiyama.
中科院分区：
文献类型：
--
作者：
Ganesh N. Pandian;R. D. Taylor;S. Junetha;A. Saha;C. Anandhakumar;T. Vaijayanthi;and H. Sugiyama.
表观遗传染色质重塑和信号传导途径在转录依赖性神经变性和长时程增强（LTP）中起着不可或缺的作用，LTP是与学习和记忆相关的细胞模型。与神经系统疾病相关的病理性表观遗传修饰具有固有的灵活性，可以通过药物干预逆转。小分子是临床医生青睐的药物，在与复杂细胞机制相关的神经系统疾病中，抑制小分子的表观遗传和/或信号通路酶已显示出临床前景。最近，具有两个或更多个功能的小分子，如序列特异性识别和信号传导途径和/或酶调节，已经显示出作为有效转录激活剂的能力。在这里，我们给出了与记忆恢复和神经退行性变相关的关键因素的平衡概述，用于调节的可用化学工具以及开发具有多功能活性的下一代小分子以治疗这种复杂的多基因相关神经系统疾病的需求。
Epigenetic chromatin remodeling and signalling pathways play an integral role in transcription dependent neurodegeneration and long-term potentiation (LTP), a cellular model associated with learning and memory. Pathological epigenetic modifications associated with neurological disorders are inherently flexible and can be reversed through pharmacological intervention. Small molecules are the favored drugs for clinicians, and in neurological disorders associated with complex cellular mechanisms, epigenetic and/or signalling pathway enzymes inhibiting small molecules have shown clinical prospects. Recently, small molecules with two or more functionalities, such as sequence-specific recognition and signalling pathways and/or enzyme modulation, have shown capabilities as efficient transcriptional activators. Here, we give a balanced overview of the key factors associated with memory recovery and neurodegeneration, available chemical tools for modulation and the demand to develop next-generation small molecules with multi-functional activities to treat such intricate, multi-gene associated neurological disorders.