and also other neurodegenerative diseases like frontotemporal dementia, Alzheimer’s and Parkinson’s disease.
First Ever Detailed Analysis
The study team explored the first molecular structure of TDP-43 aggregates from the two ALS brains using cryo-electron microscopy. To their astonishment, the team discovered unseen structural features of TDP-43 a filamentous double-spiral-shaped fold.
Moreover, the distinct structural features of the molecule indicate that TDP-43 may interact uniquely with diagnostic tools and drugs, unlike other pathological aggregates.
This explains the reason for the failures of various diagnostic compounds for ALS. The discovery thereby may open doors to progress of new-targeted medical interventions and diagnostics.
“Now that we know what the structure of aggregated TDP-43 looks like and what makes it unique, we can use it to find better ways to diagnose the disease early. We’re excited to be able to use this blueprint in our lab to start identifying compounds that bind to unique sites on TDP-43, with the aim of identifying potential therapies for further study”, says Dr. Benjamin Ryskeldi-Falcon, from the MRC Laboratory for Molecular Biology, who led the study.