Cells expressing a mutant protein, TDP-43, involved in MND pathology. Credit: Dr Rebecca San Gil from the Queensland Brain Institute
For the first time, researchers from the University of Queensland (UQ) have mapped the proteins involved in the early stages of motor neurone disease (MND).
Dr Rebecca San Gil from Associate Professor Adam Walker’s laboratory at UQ’s Queensland Brain Institute has developed a longitudinal map of proteins involved in MND across the disease trajectory, identifying potential therapeutic avenues for further research. in-depth.
“The map is a springboard for many other projects exploring proteins activated and repressed in the early, early and late stages of MND,” said Dr. San Gil.
“These proteins are biological factors that determine disease onset and progress in its development over time. We measured differences in protein levels in the brain throughout the disease trajectory and collected this information in a longitudinal map.”
The article is published in Natural communications. The map is now available to scientists around the world and will accelerate investigations into MND.
Dr. San Gil has worked in mouse models of MND to understand the mechanisms behind TDP-43 pathology in the brain, which accounts for 95% of amyotrophic lateral sclerosis (ALS) cases and 50% of lobar degeneration. frontotemporal (FTLD).
Building on 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 marked increase in protein groups 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 areas where TDP-43 aggregates.
“Short-term elevation of DNAJB5 is likely a neuron-protective mechanism aimed at controlling TDP-43 when it begins to malfunction.
“This protective response to TDP-43 requires further research as it could help us identify preventive and therapeutic approaches to MND.”
Pr/A/Prof. Walker envisions the lab will continue to follow other identified protein pathways, using gene therapy and drug repurposing, to see if they can modify or prevent disease.
More information:
Rebecca San Gil et al, A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration, Natural communications (2024). DOI: 10.1038/s41467-024-45646-9
Provided by the Queensland Brain Institute
Quote: Mapping potential pathways toward treatment of motor neuron diseases (February 20, 2024) retrieved February 20, 2024 from
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