Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.
10.1007/s12264-024-01267-2
- Author:
Tongshu LUAN
1
;
Qing LI
1
;
Zhi HUANG
1
;
Yu FENG
1
;
Duo XU
1
;
Yujie ZHOU
1
;
Yiqing HU
1
;
Tong WANG
2
Author Information
1. The Brain Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
2. The Brain Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. wangtong@shanghaitech.edu.cn.
- Publication Type:Review
- Keywords:
Amyotrophic lateral sclerosis;
Axon trafficking;
Axonopathy;
Mitochondrial defect;
Neurotrophic factor;
Protein aggregation
- MeSH:
Humans;
Amyotrophic Lateral Sclerosis/therapy*;
Animals;
Axons/metabolism*;
Mitochondria/metabolism*;
Motor Neurons/pathology*
- From:
Neuroscience Bulletin
2024;40(11):1789-1810
- CountryChina
- Language:English
-
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.
