Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.
Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany.
Cell Signal. 2014 Mar;26(3):540-8. doi: 10.1016/j.cellsig.2013.11.027. Epub 2013 Dec 3.
Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a bilateral ROCK-ERK information flow in neurons. This process is shifted towards an unidirectional crosstalk in a model of the neurodegenerative disease Spinal Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations. As both pathways are of therapeutic relevance for SMA, our results argue for a combinatorial ROCK/ERK-targeting as a future treatment strategy.
Rho-kinase (ROCK) 和细胞外信号调节激酶 (ERK) 控制肌动蛋白细胞骨架的组织，从而调节细胞形态的动态变化。在神经元中，运动过程，如轴突导向和神经突生长，需要上游途径的精细调节。在这里，我们证明了神经元中的双边 ROCK-ERK 信息流。在神经退行性疾病脊髓性肌萎缩症 (SMA) 的模型中，这个过程会向单向串扰转变，最终导致神经突生长失调。由于这两条通路都与 SMA 的治疗有关，我们的研究结果表明，联合 ROCK/ERK 靶向治疗是未来的治疗策略。
