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. 2012 Jul 5;8(7):e1002806. doi: 10.1371/journal.pgen.1002806

Figure 10. Integrated model for stress-induced TDP-1 expression.

Figure 10

TDP-1 has multiple contributions to lifespan and the cellular stress response. (A) Under normal conditions TDP-1 may function in the Insulin/IGFP pathway upstream from DAF-16 to regulate lifespan. (B) A variety of cellular stresses induce TDP-1 expression. TDP-1 induction by oxidative stress and/or the Insulin/IGF pathway is dependent on DAF-16, while induction by osmotic stress is independent of DAF-16. Misfolded proteins activate the unfolded protein response and a secondary consequence of this is the generation of oxidative stress that in turn can induce TDP-1 expression via DAF-16. The downstream consequences of tdp-1 expression are dependent on the length and strength of induction. tdp-1 mutants are sensitive to stress suggesting that TDP-1 is essential for protection against acute stress. Genetically encoded proteotoxicity from proteins like mutant TDP-43 leads to chronic induction of TDP-1 expression with negative consequences including enhanced neurodegeneration. This model also suggests that mutant proteins may act as a seed for the induction of pathological TDP-1 expression.