重组激活基因1在神经元死亡信号传导途径中指引视神经病变治疗的新靶标.doc

重组激活基因1在神经元死亡信号传导途径中：指引视神经病变治疗的新靶标？ 尽管我们已经知道转录因子，核因子kB（NF-kB）能够调节细胞的死亡和存活，但它们对中枢神经系统内细胞死亡的确切作用仍然是未知的。日本信州大学研究生医学院Takuma Hayashi教授和同事以前报道过，同型结合缺失NF-kBp50小鼠也会产生自发性视神经病变，他们研究了促凋亡因子的表达和激活能够介导p50-/-小鼠视神经病变。最近他们在《中国神经再生研究（英文版）》杂志发表的文章（2015年2月第2期）指出，重组激活基因1（RAG1）已知能够调节免疫球蛋白V（D）J重组。实验用遗传工程小鼠显示RAG1表达会参与Brn3a阳性视网膜神经节细胞的凋亡，同时也表现出其对RAG1基因转录激活P50-缺陷的具体影响。此外，鼠神经干细胞样细胞的遗传分析表明了RAG1中N-甲基-D-天冬氨酸诱导的神经元凋亡的生物学意义。最近的一项研究表明，RAG1在视神经病变中可作为一种促凋亡候选基因。这个结果或许会指引视神经病变的新治疗靶标。这些结果同时表明，在小鼠中观察到的RAG1生理意义可以延伸到人类视网膜神经节细胞存活的调节中。他们的结论是，RAG1可能参与人类青光眼性视网膜中视网膜神经节细胞的程序性细胞死亡。对RAG1在视网膜神经节细胞作用的进一步研究，预计将有助于开发人类青光眼的预防和治疗方法。 Article: Physiological significance of Rag1 in retinal ganglion cell death by Takuma Hayashi1, Toshinori Murata2 1 Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; 2 Department of Ophthalmology, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan Hayashi T, Murata T 2015 Physiological significance of Rag1 in retinal ganglion cell death. Neural Regen Res 10 2 :192-194. 欲获更多资讯Neural Regen Res Rag1 in the neuronal death signaling pathway: lead to new therapeutic targets in optic neuropathy? Although the transcription factor, nuclear factor-?B NF-?B is known to regulate cell death and survival, its precise role in cell death within the central nervous system CNS remains unknown. Prof. Takuma Hayashi, who comes from Shinshu University Graduate School of Medicine, Japan previously reported that mice with a homozygous deficiency for NF-?Bp50 spontaneously developed optic neuropathy. They examined the expression and activation of pro-apoptotic factor s that mediate optic neuropathy in p50-/- mice. Their recent published perspective article in Neural Regeneration Research Vol. 10, No. 2, 2015 points out that recombination activating gene 1 Rag1 is known to regulate the recombination of immunoglobulin V D J. Experiments with genetically engineered mice