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δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities

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Summary: This study reveals that the fragments generated by delta-secretase cleavage, APP and Tau, act additively to drive AD pathogenesis and cognitive dysfunctions. Tau(1-368) fragment enhances BACE1 expression and A beta generation, and has a more robust effect than full-length Tau, promoting the nuclear translocation of active STAT1 and increasing BACE1 and A beta production. Further mechanism involving A beta-activated kinases phosphorylating STAT1 and its association with Tau(1-368) is also discussed.

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