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Elevated β-secretase expression and enzymatic activity detected in sporadic Alzheimer disease
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A human peptidyl-prolyl isomerase essential for regulation of mitosis
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Lu, K.P.1
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Sequence-specific and phosphorylation-dependent proline isomerization: A potential mitotic regulatory mechanism
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Pinning down cell signaling, cancer and Alzheimer's disease
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Liou, Y.C., Sun, A., Ryo, A. et al. Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424, 556-561 (2003). The paper demonstrates that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer Disease.
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Liou, Y.C.1
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Thorpe, J.R., Mosaheb, S., Hashemzadeh-Bonehi, L., Cairns, N.J., Kay, J.E., Morley, S.J., and Rulten, S.L. Shortfalls in the peptidyl-prolyl cistrans isomerase protein Pin1 in neurons are associated with frontotemporal dementias. Neurobiol. Dis. 17, 237-249 (2004).
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The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production
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Pastorino, L., Sun, A., Lu, P.J. et al. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production. Nature 440, 528-534 (2006). This article is the main subject of this Viewpoint. It describes the Pin1-catalyzed prolyl isomerization as a novel mechanism to regulate APP processing and Aβ production.
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Pastorino, L.1
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Pin1 promotes production of Alzheimer's amyloid beta from beta-cleaved amyloid precursor protein
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PIN1 promoter polymorphisms are associated with Alzheimer's disease
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Segat, L., Pontillo, A., Annoni, G., Trabattoni, D., Vergani, C., Clerici, M., Arosio, B., and Crovella, S. PIN1 promoter polymorphisms are associated with Alzheimer's disease. Neurobiol Aging 2005, doi:10.1016/j. neurobiolaging.2005.11.009.
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Adaptor protein interactions: Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?
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King, G.D.1
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Transient structure of the amyloid precursor protein cytoplasmic tail indicates preordering of structure for binding to cytosolic factors
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Ramelot, T.A., Gentile, L.N., and Nicholson, L.K. Transient structure of the amyloid precursor protein cytoplasmic tail indicates preordering of structure for binding to cytosolic factors. Biochemistry 39, 2714-2725 (2000).
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Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR
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Ramelot, T.A. and Nicholson, L.K. Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR. J. Mol. Biol. 307, 871-884 (2001). The authors provide insight into the regulatory mechanisms by which phosphorylation may act as a conformational switch.
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Ando, K., Iijima, K.I., Elliott, J.I., Kirino, Y., and Suzuki, T. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid. J. Biol. Chem. 276, 40353-40361 (2001). This paper describes in detail how phosphorylation of Thr668 is likely to alter the conformation of the cytoplasmic tail to prevent binding of Fe65.
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Regulation of β-amyloid secretion by FE65, an amyloid protein precursor-binding protein
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Sabo, S.L., Lanier, L.M., Ikin, A.F., Khorkova, O., Sahasrabudhe, S., Greengard, P., and Buxbaum, J.D. Regulation of β-amyloid secretion by FE65, an amyloid protein precursor-binding protein. J. Biol. Chem. 274, 7952-7957 (1999).
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FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein
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Cam, J.A., Zerbinatti, C.V., Li, Y., and Bu, G. Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the β-amyloid precursor protein. J. Biol. Chem. 280, 15464-15470 (2005).
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APP processing is regulated by cytoplasmic phosphorylation
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Lee, M.S., Kao, S.C., Lemere, C.A., Xia, W., Tseng, H.C., Zhou, Y., Neve, R., Ahlijanian, M.K., and Tsai, L.-H. APP processing is regulated by cytoplasmic phosphorylation. J. Cell Biol. 163, 83-95 (2003). This paper uncovered an important relation between Thr668 phosphorylation and BACE1 cleavage of APP to increased Aβ production within neuronal endosomes from AD patients.
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The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein
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