| First Author | Akiyama H | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 336 |
| Issue | 2 | Pages | 521-9 |
| PubMed ID | 16139797 | Mgi Jnum | J:101001 |
| Mgi Id | MGI:3590367 | Doi | 10.1016/j.bbrc.2005.08.130 |
| Citation | Akiyama H, et al. (2005) Pin1 promotes production of Alzheimer's amyloid beta from beta-cleaved amyloid precursor protein. Biochem Biophys Res Commun 336(2):521-9 |
| abstractText | Here we show that prolyl isomerase Pin1 is involved in the Abeta production central to the pathogenesis of Alzheimer's disease. Enzyme immunoassay of brains of the Pin1-deficient mice revealed that production of Abeta40 and Abeta42 was lower than that of the wild-type mice, indicating that Pin1 promotes Abeta production in the brain. GST-Pin1 pull-down and immunoprecipitation assay revealed that Pin1 binds phosphorylated Thr668-Pro of C99. In the Pin1-/- MEF transfected with C99, Pin1 co-transfection enhanced the levels of Abeta40 and Abeta42 compared to that without Pin1 co-transfection. In COS7 cells transfected with C99, Pin1 co-transfection enhanced the generation of Abeta40 and Abeta42, and reduced the expression level of C99, facilitating the C99 turnover. Thus, Pin1 interacts with C99 and promotes its gamma-cleavage, generating Abeta40 and Abeta42. Further, GSK3 inhibitor lithium blocked Pin1 binding to C99 by decreasing Thr668 phosphorylation and attenuated Abeta generation, explaining the inhibitory effect of lithium on Abeta generation. |
