Deficits in axonal transport precede ALS symptoms in vivo.
ALS is a fatal neurodegenerative disease characterized by selective motor neuron death resulting in muscle paralysis. Mutations in superoxide dismutase 1 (SOD1) are responsible for a subset of familial cases of ALS. Although evidence from transgenic mice expressing human mutant SOD1(G93A) suggests that axonal transport defects may contribute to ALS pathogenesis, our understanding of how these relate to disease progression remains unclear. Using an in vivo assay that allows the characterization of axonal transport in single axons in the intact sciatic nerve, we have identified clear axonal transport deficits in presymptomatic mutant mice. An impairment of axonal retrograde transport may therefore represent one of the earliest axonal pathologies in SOD1(G93A) mice, which worsens at an early symptomatic stage. A deficit in axonal transport may therefore be a key pathogenic event in ALS and an early disease indicator of motor neuron degeneration.
Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, United Kingdom.
Lynsey G
LG
Bilsland
Erik
E
Sahai
Gavin
G
Kelly
Matthew
M
Golding
Linda
L
Greensmith
Giampietro
G
Schiavo
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D018450:Disease Progression; D007734:Kymography; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D009046:Motor Neurons / Q000473:pathology* / Q000502:physiology; D009154:Mutation / Q000235:genetics; D012584:Sciatic Nerve / Q000166:cytology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1