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Published on: February 10, 2020
TDP-43 protein interactome informs about perturbed canonical pathways and may help develop personalized medicine
Benjamin R Helmold1, Kate E Pauss1, P Hande Ozdinler2
1Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
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. Our approach proposes that personalized medicine approaches, which focus on perturbed cellular mechanisms would be feasible in the near future.
Insights
Transactive response DNA binding protein of 43 kDa (TDP-43) pathology is linked to protein interactions. Targeting these interactions and cellular pathways may enable personalized medicine for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Transactive response DNA binding protein of 43 kDa (TDP-43) pathology is prevalent in neurodegenerative diseases.
- Protein-protein interactions involving TDP-43 are implicated in disease pathogenesis.
- Understanding these interactions is crucial for developing effective treatments.
Purpose of the Study:
- To identify TDP-43-binding proteins across different domains.
- To correlate TDP-43 interactions with specific canonical cellular pathways.
- To explore potential therapeutic targets for TDP-43-related neurodegeneration.
Main Methods:
- Investigated TDP-43 protein interactions within distinct cellular domains.
- Utilized pathway analysis to link protein interactions to cellular mechanisms.
- Reviewed existing compounds for their potential to modulate identified pathways.
Main Results:
- Identified key cellular events associated with TDP-43 binding proteins in specific domains.
- Correlated TDP-43 interactions with relevant canonical pathways.
- Highlighted previously identified compounds capable of modulating these pathways.
Conclusions:
- TDP-43 protein interactions play a significant role in neurodegenerative pathology.
- Perturbed cellular pathways offer potential targets for therapeutic intervention.
- Personalized medicine approaches focusing on cellular mechanisms are a promising future direction.
