Figure 11. TDP‐43 interactome analysis highlights pathological pathways and therapeutic effect of HDAC6 inhibition.

• A
  Scheme illustrating set‐up of TDP‐43 interactome analysis.
• B
  Ranked GO enrichment analysis of mutant versus wild‐type TDP‐43 interactors indicates nuclear depletion of mutant TDP‐43.
• C
  More detailed GO analysis further highlights nuclear depletion of mutant TDP‐43 and potential loss‐of‐function mechanisms.
• D
  Several axonal transport factors differentially interact with mutant versus wild‐type TDP‐43.
• E
  The mutant TDP‐43 interactome is depleted for nuclear transport factors and enriched for proteostasis factors, in line with its observed nuclear depletion and cytoplasmic pathological alterations.
• F
  Scheme illustrating the effect of HDAC6 inhibition on mutant TDP‐43 phenotypes.
• G, H
  Ranked GO enrichment analysis highlights the effect of HDAC6 inhibition on the mutant TDP‐43 interactome, in line with its restored nuclear localization.