Ohtake Yosuke, Hayat Umar, Li Shuxin
Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA, USA.
Neural Regen Res. 2015 Sep;10(9):1363-8. doi: 10.4103/1673-5374.165496.
The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to control the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in conditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Importantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.
在发育过程中,所有神经元的内在生长能力都会下降,尽管有些神经元可能比其他神经元生长得更好。大量细胞内信号蛋白和转录因子已被证明可调节成熟神经元的内在生长能力。其中,PI3激酶/Akt信号通路对于控制轴突伸长很重要。作为该信号通路的负调节因子,肿瘤抑制因子磷酸酶和张力蛋白同源物(PTEN)似乎对控制幼年和成年神经元的再生能力至关重要。本综述将重点关注通过抑制PTEN促进轴突再生和神经修复的最新研究进展,以及阻断这种磷酸酶治疗神经疾病的潜力。通过条件性敲除小鼠中的PTEN基因、短发夹RNA敲低或包括给予选择性PTEN拮抗剂肽在内的药理学方法阻断PTEN,可在患有中枢神经系统损伤的幼年或成年啮齿动物中刺激不同程度的轴突再生。重要的是,损伤后抑制PTEN可以促进成年中枢神经系统损伤后的轴突生长和功能恢复。