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For the first time, University of Queensland (UQ) researchers have mapped a protein found in the early stages of motor neurone disease (MND).

Dr Rebecca San Gil, from Associate Professor Adam Walker’s lab at UQ’s Queensland Brain Institute, has produced a longitudinal map of proteins involved in MND, identifying potential therapeutic avenues for further investigation.

“The map is a springboard for many projects looking for proteins that are activated and repressed during the early, early and late stages of MND,” said Dr San-Gil.

“These proteins are biological factors that drive the onset of disease and drive its progression over time.

“We measured differences in protein levels in the brain throughout the course of the disease and assembled this information into a longitudinal map.”

This map is now available to scientists around the world and will accelerate MND research.

Dr. San-Gil is working in mouse models of MND to understand the mechanisms driving TDP-43 pathology in the brain, which accounts for 95% of amyotrophic lateral sclerosis (ALS) cases and 50% of frontotemporal lobar degeneration (FTLD).

In building the mapping project, Dr. San-Gil chose to focus on a protein-folding factor called DNAJB5.

“Before the onset of MND in mouse models, we observed a significant increase in protein groups that are responsible for physically assisting the protein folding process.

“One of these ‘chaperone’ proteins, DNAJB5, was particularly abundant early on, sparking our curiosity about its role in disease progression.

“In human brain tissue, we found DNAJB5 enriched in regions where TDP-43 aggregates.

“The short-term elevation of DNAJB5 is likely a protective mechanism by neurons in an attempt to control TDP-43 as it begins to degenerate.

“This protective response to TDP-43 warrants further investigation as it may help us identify preventive and therapeutic approaches for MND.”

A/Professor Walker envisions the lab will continue to pursue other identified protein pathways, using gene therapy and repurposing drugs, to see if they can reverse or prevent disease.

It was published in the paper. Nature Communications.

Mapping TDP was a collaborative project with researchers from Macquarie University, the University of Auckland and the Children’s Medical Research Institute.

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