Proceedings of the National Academy of Sciences · 2010 · 409 citations · 32 references
Motor DysfunctionNeurological DisorderIntact Sciatic NerveSocial SciencesNeurobiology Of DiseaseNeurologyNeuropathologyMotor Neuron DiseasesSuperoxide Dismutase 1Als PathogenesisNeurodegenerationCell BiologyNeurodegenerative DiseasesAmyotrophic Lateral SclerosisNeurophysiologyNeuroanatomyDegenerative DiseaseNeuroscienceMolecular NeurobiologyCentral Nervous SystemMedicine
ALS is a fatal neurodegenerative disease marked by selective motor neuron death and muscle paralysis, with SOD1 mutations responsible for some familial cases, and evidence from mutant SOD1 mice indicates axonal transport defects may contribute to disease pathogenesis, though their relation to progression remains unclear. In vivo analysis of single axons in the sciatic nerve of SOD1(G93A) mice revealed presymptomatic deficits in axonal transport, with retrograde transport impairment emerging early and worsening at symptomatic stages, suggesting that axonal transport deficits are a key pathogenic event and early indicator of motor neuron degeneration.
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.
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Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ
Chunjie Zhao, Junko Takita, Yosuke Tanaka et al. · Cell · 2001 · 758 citations · Full text