Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030, USA.
Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030, USA.
Neurosci Lett. 2021 Nov 20;765:136260. doi: 10.1016/j.neulet.2021.136260. Epub 2021 Sep 21.
Projection neurons of the mammalian central nervous system (CNS) do not spontaneously regenerate axons which have been damaged by an injury or disease, often leaving patients with permanent disabilities that affect motor, cognitive, or sensory functions. Although several molecular targets which promote some extent of axon regeneration in animal models have been identified, the resulting recovery is very limited, and the molecular mechanisms underlying the axonal regenerative failure in the CNS are still poorly understood. One of the most studied targets for axon regeneration in the CNS is the mTOR pathway. A number of developmentally regulated genes also have been found to play a role in CNS axon regeneration. Here, we found that Transcriptional Elongation Factor A Like 3 (Tceal3), belonging to the Bex/Tceal transcriptional regulator family, which also modulates the mTOR pathway, is developmentally upregulated in retinal ganglion cell (RGCs) projection CNS neurons, and suppresses their capacity to regenerate axons after injury.
哺乳动物中枢神经系统 (CNS) 的投射神经元不会自发地再生因损伤或疾病而受损的轴突,这常常使患者留下影响运动、认知或感觉功能的永久性残疾。尽管已经确定了几个促进动物模型中一定程度轴突再生的分子靶点,但由此产生的恢复非常有限,并且中枢神经系统中轴突再生失败的分子机制仍知之甚少。中枢神经系统中轴突再生最受研究的靶点之一是 mTOR 途径。一些发育调控基因也被发现在中枢神经系统轴突再生中发挥作用。在这里,我们发现转录延伸因子 A 样 3 (Tceal3) 属于 Bex/Tceal 转录调节因子家族,也调节 mTOR 途径,在视网膜神经节细胞 (RGCs) 投射 CNS 神经元中呈发育性上调,并抑制它们在受伤后再生轴突的能力。