Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.
Neurosci Bull
; 2024 Aug 04.
Article
en En
| MEDLINE
| ID: mdl-39097850
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.
Texto completo:
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Banco de datos:
MEDLINE
Idioma:
En
Revista:
Neurosci Bull
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China