上海科技大学王彤研究组总结肌萎缩侧索硬化症背后的轴突病理。相关论文于2024年8月4日在线发表于国际学术期刊《神经科学通报》。

研究人员强调了轴突病理在肌萎缩侧索硬化症（ALS）进展中的作用，该进展受多种因素的共同影响，包括运输机制缺陷、蛋白质聚集和线粒体功能障碍。细胞内运输功能障碍是由于微管、分子马达和适配蛋白的破坏，被认为是疾病进展的关键因素。TDP-43、FUS、SOD1和二肽重复蛋白的异常聚集进一步加剧了神经毒性。

线粒体缺陷导致ATP耗竭、氧化应激和钙离子（Ca2+）失衡，这被认为是导致神经肌肉连接丧失和轴突病理的关键因素。通过包括神经营养治疗在内的干预措施来缓解这些缺陷，具有治疗潜力。协作研究努力旨在揭示ALS的复杂性，为针对多种病理机制的全面干预开辟了途径。

研究人员表示，ALS是一种复杂的神经退行性疾病，其特征是逐渐加重的轴突病理，导致运动神经元的退化，破坏神经信号传导和运动控制。

附：英文原文

Title: Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights

Author: Luan, Tongshu, Li, Qing, Huang, Zhi, Feng, Yu, Xu, Duo, Zhou, Yujie, Hu, Yiqing, Wang, Tong

Issue&Volume: 2024-08-04

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca2+ imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.

DOI: 10.1007/s12264-024-01267-2

Source: https://link.springer.com/article/10.1007/s12264-024-01267-2