TDP-43 protein interactome informs about perturbed canonical pathways and may help develop personalized medicine approaches for patients with TDP-43 pathology
Benjamin Helmold, Kate E. Pauss, P. Hande Özdi̇nler
Abstract
Transactive response DNA binding protein of 43 kDa (TDP-43) pathology is a common proteinopathy observed among a broad spectrum of patients with neurodegenerative disease, regardless of the mutation. This suggests that protein–protein interactions of TDP-43 with other proteins may in part be responsible for the pathology. To gain better insights, we investigated TDP-43-binding proteins in each domain and correlated these interactions with canonical pathways. These investigations revealed key cellular events that are involved and are important at each domain and suggested previously identified compounds to modulate key aspects of these canonical pathways, suggesting that personalized medicine approaches that focus on perturbed cellular mechanisms are feasible in the near future. Teaser The location of the mutation impacts protein–protein interactions, downstream signaling cascade and canonical pathways. To develop precision medicine with personalized medicine approaches, one must consider not only the mutated gene but also the interactome dynamics.