Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis - PubMed
5 hours ago
- #ALS
- #Neurodegeneration
- #Axonal Transport
- ALS is a fatal neurodegenerative disease involving loss of motor neurons.
- Axonal transport impairment is proposed as an early, convergent upstream mechanism in ALS pathogenesis.
- Transport deficits appear in presymptomatic stages across various ALS models (e.g., SOD1, TDP-43, FUS, C9orf72).
- Human data from iPSC-derived motor neurons and neuroimaging support early transport dysfunction in familial and sporadic ALS.
- Diverse ALS mutations disrupt trafficking machinery, leading to cargo delivery and clearance issues in motor neurons.
- This model explains selective motor neuron vulnerability, neuromuscular junction degeneration, and downstream pathologies.
- It suggests potential presymptomatic biomarkers and therapeutic strategies targeting transport restoration.