FRAT1 peptide decreases Aβ production in swAPP751 cells

[摘要]

Recently, LiCl has been shown to inhibit amyloid β peptide secretion in association with diminished glycogen synthase kinase β (GSK3β) activity. However, it remains unclear if direct inhibition of GSK3β activity will result in decreased Aβ production. requently earranged in dvanced -cell lymphomas (FRAT1) protein is a negative regulator of GSK3α/β kinase activity. To examine whether direct inhibition of GSK3α/β kinase activity can lower Aβ production, a FRAT1 peptide was expressed in swAPP₇₅₁ cells that produce high levels of Aβ. Our data demonstrate that cellular expression of FRAT1 peptide in swAPP₇₅₁ cells increases both GSK3α and β phosphorylation on Ser21 and Ser9, respectively, while inhibiting kinase activity of both isoforms. Moreover, as a result of FRAT1 expression, the production of both total Aβ and Aβ_1-42 was significantly decreased. Thus, we provide evidence that direct regulation of GSK3α/β by FRAT1 peptide significantly decreases Aβ production in swAPP₇₅₁ cells.

[学科分类] 生物化学/生物物理

[关键词] FRAT;Glycogen synthase kinase;Amyloid;Amyloid precursor protein;Alzheimer's disease;Kinase activity