Kwon Min Jee, Kim Jeong-Hoon, Kim TaeSoo, Lee Sung Bae
Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea.
Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Daejeon 34141, Republic of Korea.
Pharmacol Res. 2017 May;119:169-177. doi: 10.1016/j.phrs.2017.02.003. Epub 2017 Feb 4.
Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neurodegenerative diseases, even before the occurrence of prominent neuronal death. However, until recently, the primary focus of studies regarding many neurodegenerative diseases has been on the massive cell death occurring at the late stages of disease progression. Thus, our understanding on early neuropathy in these diseases remains relatively limited. The complicated nature of various neuropathic features manifested early in neurodegenerative diseases suggests the involvement of a system-wide transcriptional regulation and epigenetic control. Epigenetic alterations and consequent changes in the neuronal transcriptome are now begun to be extensively studied in various neurodegenerative diseases. Upon the catastrophic incident of neuronal death in disease progression, it is utterly difficult to reverse the deleterious defects by pharmacological treatments, and therefore, therapeutics targeting the system-wide transcriptional dysregulation associated with specific early neuropathy is considered a better option. Here, we review our current understanding on the system-wide transcriptional dysregulation that is likely associated with early neuropathy shown in various neurodegenerative diseases and discuss the possible future developments of pharmaceutical therapeutics.
大量研究报告了众多细胞特征和过程在动物整个生命周期中正确维持神经元形态和功能方面的重要作用。在动物出现明显的神经元死亡之前，它们体内平衡的任何改变似乎都与神经元衰老和各种神经退行性疾病的发病机制密切相关。然而，直到最近，许多关于神经退行性疾病的研究主要集中在疾病进展后期发生的大量细胞死亡上。因此，我们对这些疾病早期神经病变的了解仍然相对有限。神经退行性疾病早期表现出的各种神经病变特征的复杂性表明，这涉及全系统的转录调控和表观遗传控制。表观遗传改变以及随之而来的神经元转录组变化，目前已开始在各种神经退行性疾病中得到广泛研究。在疾病进展过程中发生神经元死亡这一灾难性事件后，通过药物治疗完全难以逆转有害缺陷，因此，针对与特定早期神经病变相关的全系统转录失调的治疗方法被认为是更好的选择。在此，我们回顾了目前对可能与各种神经退行性疾病中出现的早期神经病变相关的全系统转录失调的理解，并讨论了药物治疗未来可能的发展方向。
