Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are prototypical motor neuron diseases that result in progressive weakness as a result of motor neuron dysfunction and death.
Lower motor neuron dysfunction is one of the most debilitating neurological conditions and, as such, significantly impacts on the quality of life of affected individuals.
Though much work has been done in both diseases to identify the cellular mechanisms of motor neuron dysfunction, once motor neurons have died, one of potential therapies to restore function would be through the use of cellular transplantation.
Finally we looked at the addition of a novel Transcranial magnetic stimulation (TMS) technique as an objective biomarker of upper motor neuron dysfunction, to further improve the current criteria.
For their classification system, people with spina bifida were not eligible unless they also had evidence of upper motor neuron dysfunction, caused by associated hydrocephalus.
However, it is unclear if BBB/BSCB disruption appears prior to motor neuron degeneration or as result of motor neuron dysfunction.
Further genetic analysis using this model as a paradigm for ALS is likely to provide insights into pathways that contribute to motor neuron dysfunction and death in ALS.
Notably, functional impairment of other endolysosomal-associated proteins such as ESCRT subunit and Rab7 also causes motor neuron dysfunction [60], [61].
We did not observe hindlimb paralysis, increased seizure activity, or other signs of nervous system or motor neuron dysfunction in the majority of animals that died prematurely.
6 In ALS, upper motor neuron dysfunction causes spasticity, whereas lower motor neuron dysfunction leads to muscle wasting, weakness, and fasciculation.
