[Dysfunction of dynactin 1 in motor neuron degeneration].

Dynactin 1 is an axon motor protein regulating retrograde transport of various proteins and vesicles including autophagosome. We previously demonstrated that the expression levels of dynacin 1 are markedly reduced in spinal motor neurons of sporadic ALS patients. We generated a Caenorhabditis elegans model in which the expression of dnc-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed the impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration.