Figure 8 | Cell Death & Disease

Figure 8

From: TGF-β induces TIAF1 self-aggregation via type II receptor-independent signaling that leads to generation of amyloid β plaques in Alzheimer's disease

Figure 8

Schematic summary of TGF-β1-induced TIAF1 self-aggregation. (a) Under physiological conditions, TGF-β1 signals via Smad2/3/4 or hyaluronidase Hyal-2.14 Additionally, TGF-β1 stimulates the binding of TIAF1 with Smad4 for relocating to the nuclei to regulate gene transcription. Smad4 prevents TIAF1 self-aggregation. (b) Altered TGF-β signaling is expected under pathological conditions. TGF-β1 signals via TGF-β receptors or Hyal-2 for APP fragmentation and TIAF1 self-aggregation. Supporting evidence shows that TIAF1 binds and stabilizes membrane Thr668-phosphorylated APP. TGF-β1 reduces the binding, thus leading to APP de-phosphorylation. The dephosphorylated APP undergoes degradation and generation of Aβ monomer, AICD and amyloid fibrils. TIAF1 aggregates form complexes with amyloid fibrils for apoptosis and gradual formation of TIAF1/Aβ plaques. Smad4 may block TIAF1 aggregation. Alternatively, TIAF1 aggregates bind cytosolic Smad4 to prevent nuclear accumulation and apoptosis. Thus, a balanced status of phosphorylation of APP is critical in determining plaque formation

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