Liu Da-Zhi, Ander Bradley P
Department of Neurology and the MIND Institute, University of California at Davis, Sacramento, CA 95817, USA.
ScientificWorldJournal. 2012;2012:491737. doi: 10.1100/2012/491737. Epub 2012 Apr 1.
Since publishing our earlier report describing a strategy for the treatment of central nervous system (CNS) diseases by inhibiting the cell cycle and without disrupting neurogenesis (Liu et al. 2010), we now update and extend this strategy to applications in the treatment of cancers as well. Here, we put forth the concept of "aberrant cell cycle diseases" to include both cancer and CNS diseases, the two unrelated disease types on the surface, by focusing on a common mechanism in each aberrant cell cycle reentry. In this paper, we also summarize the pharmacological approaches that interfere with classical cell cycle molecules and mitogenic pathways to block the cell cycle of tumor cells (in treatment of cancer) as well as to block the cell cycle of neurons (in treatment of CNS diseases). Since cell cycle inhibition can also block proliferation of neural progenitor cells (NPCs) and thus impair brain neurogenesis leading to cognitive deficits, we propose that future strategies aimed at cell cycle inhibition in treatment of aberrant cell cycle diseases (i.e., cancers or CNS diseases) should be designed with consideration of the important side effects on normal neurogenesis and cognition.
自从我们发表了早期报告,描述了一种通过抑制细胞周期且不破坏神经发生来治疗中枢神经系统(CNS)疾病的策略(Liu等人,2010年),我们现在将这一策略更新并扩展到癌症治疗应用中。在此,我们提出“异常细胞周期疾病”的概念,通过关注每种异常细胞周期重新进入中的共同机制,将表面上两种不相关的疾病类型——癌症和中枢神经系统疾病——囊括在内。在本文中,我们还总结了干扰经典细胞周期分子和促有丝分裂途径以阻断肿瘤细胞(用于癌症治疗)以及神经元细胞周期(用于中枢神经系统疾病治疗)的药理学方法。由于细胞周期抑制也会阻断神经祖细胞(NPC)的增殖,从而损害脑内神经发生导致认知缺陷,我们建议未来针对异常细胞周期疾病(即癌症或中枢神经系统疾病)治疗中细胞周期抑制的策略设计应考虑到对正常神经发生和认知的重要副作用。