High-resolution imaging of synaptic integrity in MND

Synapse loss is an early feature of most neurodegenerative diseases, including MND, yet we do not have a clear understanding of the underlying mechanisms. By using high-resolution imaging and proteomic screening, we hope to identify the mechanisms driving synapse loss in MND and highlight potential new therapeutic targets. We have shown that synapse loss occurs in the frontal cortex of some MND patients and greater synapse loss associates with poorer cognitive function. To build on this, we are now running unbiased proteomic screening of synaptically-enriched human brain fractions to identify the pathways and proteins that are disrupted in MND. These exciting new targets will be validated in human tissue before moving into model systems to assess their role on synaptic toxicity.