神经退行性疾病中轴突运输障碍的机制

Mechanisms of Axonal Transport Deficits in Neurodegenerative Diseases

临床上许多神经退行性疾病包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等,主要表现为致病蛋白的蓄积和细胞器的异常定位。这一病理特征可能与神经元中轴突运输障碍有关,轴突运输异常可能导致致病蛋白不能定向转运到特定部位降解,细胞器不能运至指定区域发挥正常生理功能,甚至轴突运输障碍极有可能是此类疾病的早期病理事件,并逐渐发展成轴突完整性的丧失与退行性改变。在此,我们对多种常见的神经退行性疾病中轴突运输障碍的发生发展机制进行探讨,为后续的基础研究提供新思路。

Numerous neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,exhibit a common pathophysiological hallmark of aberrant protein aggregation and organelle mislocalization.These pathological manifestations are hypothesized to stem from disruptions in axonal transport within neurons,resulting in the impaired targeting of pathological proteins for degradation and the misplacement of organelles crucial for normal cellular functions.This review aims to illustrate the mechanisms responsible for axonal transport deficits in various prevalent neurodegenerative diseases,suggesting that these deficits are typically early pathological occurrences that ultimately result in the deterioration of axonal integrity and degenerative alterations.The review may offer novel insights for future fundamental research endeavors.