Pharmacological intervention of early neuropathy in neurodegenerative diseases.
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.
Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea.
Min Jee
MJ
Kwon
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.
Jeong-Hoon
JH
Kim
Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Republic of Korea.
TaeSoo
T
Kim
Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea. Electronic address: sblee@dgist.ac.kr.
Sung Bae
SB
Lee
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015533:Transcriptional Activation / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects
Early neuropathy; Epigenetic changes; Neurodegenerative disease; Transcriptional dysregulation