Understanding the pre-synapse

Summary

In MND, and Frontotemporal Dementia (FTD), we know several proteins are found in the wrong place in motor neurons. However, other proteins might also be in the wrong place in the neuron and at synapses, which are small gaps between neighbouring neurons that are essential for neurons to communicate. Messages are packaged in the “pre-synapse” of one neuron and sent across the synapse to the next neuron. This process relies heavily on proteins being in the correct place. If neurons are unable to communicate through synapses, this can lead to neuron death.

Using a highly innovative approach called spatial proteomics, Dr Dafinca will isolate the different cellular compartments present at the motor neuron pre-synapse and use a sophisticated technique to map the location of proteins within each compartment. This will be supplemented by mapping changes in the expression of RNA (messengers that encode proteins). By comparing motor neurons from people living with MND and FTD with healthy controls, differences in protein and RNA expression will be identified.

Why this research is important

This study will be the first to identify changes in the placements of all proteins in MND axons that might contribute to neuron death. Successfully using this technique will greatly improve understanding of how protein disruptions affect MND and could lead to the discovery of new treatment targets.