PubMed: 27094130

Title
Inhibition of death-associated protein kinase 1 attenuates the phosphorylation and amyloidogenic processing of amyloid precursor protein.
Journal
Human molecular genetics
Volume
25
Issue
None
Pages
2498-2513
Date
2016-06-15
Authors
Chen CH | Ho Lee T | Kim BM | Suh J | Tanzi RE | You MH

Evidence 8623e84354

In contrast, the DAPK1 fragments from 1 to 1423, from 637 to 1423 and from 848 to 1423 efficiently bound to APP, suggesting that the death domain (1271–1423, DD) is likely bound to APP (Fig. 4F).

Evidence 3e0bb7878b

DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ.

Evidence 3b5ac1e062

Furthermore, DAPK1-induced APP phosphorylation was suppressed when DAPK1 ΔDD was introduced (Fig. 4G), indicating that DAPK1 regulates Aβ secretion through APP Thr668 phosphorylation.

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