Identification and characterisation of RNA-protein interaction in pathological aggregates of TDP-43 in MND

Identifying the protein and RNA composition of TDP-43 inclusions to find potential targets to mitigate the effects of aggregation are crucial. A recent paper highlighted the use of a method to quantify RNA-binding proteome dynamics and RNA-protein interaction across different conditions by integrating RNA-sequencing and mass spectrometry (MS)-based proteomics. This methodology can capture significant new insight into the complex molecular composition of these hallmark TDP-43 inclusions. Coupled with an immunoprecipitation method, the known and novel identification of specific mRNA that are involved in the translocation and aggregation of TDP-43 can be achieved. With this knowledge, a therapeutic approach using RNA interference can be designed to target specific mRNA for degradation to their reverse or prevent formation of aggregation.