Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Pharmacol Res. 2018 Jun;132:135-148. doi: 10.1016/j.phrs.2018.04.014. Epub 2018 Apr 20.
The accumulation of somatic and genetic mutations which altered the structure and coding information of the DNA are the major cause of neurological disorders. However, our recent understanding of molecular mechanisms of 'epigenetic' phenomenon reveals that the modifications of chromatin play a significant role in the development and severity of neurological disorders. These epigenetic processes are dynamic and reversible as compared to genetic ablations which are stable and irreversible. Therefore, targeting these epigenetic processes through small molecule modulators are of great therapeutic potential. To date, large number of small molecule modulators have been discovered which are capable of altering the brain pathology by targeting epigenetic enzymes. In this review, we shall put forward the key studies supporting the role of altered epigenetic processes in neurological disorders with especial emphasis on neurodegenerative disorders. A few small molecule modulators which have been shown to possess promising results in the animal model system of neurological disorders will also be discussed with future perspectives.
体细胞和遗传突变的积累改变了 DNA 的结构和编码信息，是神经紊乱的主要原因。然而，我们最近对“表观遗传”现象的分子机制的理解表明，染色质的修饰在神经紊乱的发展和严重程度中起着重要作用。与稳定且不可逆的遗传缺失相比，这些表观遗传过程是动态和可逆的。因此，通过小分子调节剂靶向这些表观遗传过程具有很大的治疗潜力。迄今为止，已经发现了大量的小分子调节剂，它们能够通过靶向表观遗传酶来改变大脑病理学。在这篇综述中，我们将提出支持表观遗传过程改变在神经紊乱中起作用的关键研究，特别强调神经退行性疾病。我们还将讨论一些在神经紊乱的动物模型系统中显示出有前景的结果的小分子调节剂，并展望未来。
