March 2017: Dr Lyndsay Murray and her team shed light on factors regulating motor neuron vulnerability.
In motor neuron disease, not all motor neurons appear to be affected in the same way. Some are lost very early in the disease, while some persist even at late stages.
The reasons for this are unclear; however, understanding this may provide new targets for therapeutics to slow motor neuron degeneration.
Here, we re-analysed data from 4 independent screens on motor neurons which were found to be vulnerable or resistant in different subtypes of motor neuron disease and identified transcripts which were common across screens.
We have used a drosophila model of ALS to perform an in vivo validation of these transcripts. One of the common transcripts was alpha-synuclein (SNCA), which was consistently expressed at lower levels in vulnerable motor neurons.
We increased SNCA levels in a mouse model of motor neuron disease and this resulted in an extension in survival and reduction in motor neuron pathology. Collectively, these results demonstrate that this approach can identify disease modifiers that can reduce disease severity in models of motor neuron disease and potentially identify new therapeutic targets.