Deciphering changes in intracellular signals during axon degeneration

在这项研究中，我们的具体目标是破译调节轴突变性过程的机制和因素，轴突变性是在包括阿尔茨海默病在内的各种神经系统疾病中观察到的标志性表型。我们在原代培养的神经元中建立了谷氨酸兴奋性毒性诱导的轴突变性系统，发现p150 Glued和动力蛋白中间链（DIC），两者都是逆行运输动力蛋白-动力蛋白复合物的主要成分，微管稳定和抑制p53反式激活调节轴突变性过程，包括轴突变性。由于谷氨酸兴奋性毒性与各种神经功能缺损有关，我们的研究结果确定了逆行转运蛋白、微管动力学和肿瘤抑制蛋白p53作为神经系统疾病中观察到的轴突变性的新型细胞内信号调节剂。

In this study, our specific aim is to decipher mechanisms and factors that regulate the process of axon degeneration, a hallmark phenotype observed in various neurological disorders including Alzheimer’s disease. We developed aglutamate excitotoxicity-induced axon degeneration system in primary neuronal culturesand found that p150Glued and dynein intermediate chain (DIC), both of which are major components of the retrograde transport dynein-dynactin complex, microtubule stabilization, and inhibition of p53 transactivation regulate the process of axondegeneration including axon degeneration. As glutamate excitotoxicity is implicated in various neurological deficits, our findings identify retrograde transport proteins,microtubule dynamics, and tumor suppressor protein p53 as novel intracellular signalingmodulators of axon degeneration observed in neurological disorders.