Ekshyyan Oleksandr, Aw Tak Yee
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Front Biosci. 2004 May 1;9:1567-76. doi: 10.2741/1357.
Programmed cell death or apoptosis is a physiologically important process in neurogenesis wherein approximately 50% of the neurons apoptose during maturation of the nervous system. However, premature apoptosis and/or aberrations in apoptosis control contribute to the pathogenesis of a variety of neurological disorders including acute brain injury such as trauma, spinal cord injury, ischemic stroke and ischemia/reperfusion as well as chronic disease states such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, spinal muscular atrophy, and diabetic neuropathy. The current review will focus on two major topics, namely, the general concepts of our current understanding of the apoptosis death machinery, its mediators and regulation, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. This knowledge of apoptosis mechanisms will underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program.
程序性细胞死亡或凋亡是神经发生过程中一个重要的生理过程,在神经系统成熟过程中,约50%的神经元会发生凋亡。然而,过早凋亡和/或凋亡控制异常会导致多种神经系统疾病的发病机制,包括急性脑损伤,如创伤、脊髓损伤、缺血性中风和缺血/再灌注,以及慢性疾病状态,如阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症、脊髓性肌萎缩症和糖尿病性神经病变。本综述将聚焦于两个主要主题,即我们目前对凋亡死亡机制、其介导因子和调节的总体认识,以及异常凋亡与神经退行性疾病发生之间的关系。这种对凋亡机制的认识将为开发针对控制神经元凋亡死亡程序的新型治疗策略和治疗方式奠定基础。