CMT is the most common inherited neurological disorder. We are focusing on mechanisms responsible for CMT type 2, which specifically affects motor and sensory axons. Mutations of 5 different amino-acyl tRNA synthetases cause CMT2. Curiously, although the only shared function of these amino-acyl tRNA synthetases is support of mRNA translation, the prevailing view is that the mutated proteins have little effect on translation but cause disease by neomorphic toxic effects unrelated to protein synthesis. We are exploring a hypothesis that challenges this point of view employing in vivo, in vitro, and in silico approaches.
- Investigators: Alec Smith, Mark Bothwell, Matt Childers