P-amyloid precursor protein

APP P-amyloid precursor protein 21q21 Dominant AP production (ApT AP AP ratioT)/aggregation... 

Ehehalt, R., KeUer, P., Haass, C., Thiele, C., Simons, K. (2003) Amyloidogenic processing of the Alzheimer P-amyloid precursor protein depends on lipid rafts. J. Cell. Biol., 160, 113-123. 

Edbauer, D., Willem, M., Lammich, S., Steiner, H., Haass, C. (2002) Insuhn-degrading enzyme rapidly removes the P-amyloid precursor protein intracellular domain (AlCD). J. Biol. Chem., Ill, 13389-13393. 

Furukawa K, Barger SW, Blalock EM, Mattson MP. Activation of K+ channels and suppression of neuronal activity by secreted P-amyloid-precursor protein. Nature 1996 379 74-78. 

Meziane H, Dodart JC, Mathis C, et al. Memory-enhancing effects of secreted forms of the p-amyloid precursor protein in normal and amnestic mice. Proc Natl Acad Sci USA 1998 95 12,683-12,688. 

Since PTB domains adopt the same fold as PH domains, J. Schlessinger has suggested that the PTB domain may be another class of PH domain, a relationship that was overlooked because of the absence of sequence homologies.52 This classification is supported by differences between PTB domains and classical SH2 domains. The crystal structure of the phosphotyrosine-binding domain (PTB) of a human, neuron-specific peptide (XI1) that contains a C-terminal PTB domain, provides relevant information.53 With its PTB domain, this peptide binds to the cytoplasmic domain of the p-amyloid precursor protein (P-APP), found in the brain of patients with Alzheimer s disease. The domain with which the peptide interacts is an internalization motif of P-APP (Fig. 3.4). 

P-amyloid precursor protein aB-crystallin Capulet Chd64 CGI 0724 Ebl... 

Ringheim GE, Szcepanik AM, Burgher KL, et al. Transcriptional inhibition of the P-amyloid precursor protein by interferon-gamma. Biochem Biophys Res Commun 1996 224 246-51. 

The major constituent of the extracellular plaques is amyloid -protein (Ap), which aggregates into 8 nm filaments. Ap is a peptide of 40 or 42 amino acid residues and is proteolytically derived from a transmembrane glycoprotein known as P-amyloid precursor protein (jSAPP). The enzymes that cleave APP to A/3 are known as sec-retases. SAPP is widely expressed, particularly in brain, and its gene has been localized to chromosome 21q. Two major observations have aided in understanding the role of Ap peptides in the pathology of Alzheimer s disease. The first is that patients with Down syndrome have trisomy 21... 

Arribas, J, Lopez-Casillas, F., and Massague, J. (1997). Role of the juxtamembrane domains of the transforming growth factor-a precursor and the P-amyloid precursor protein in regulated ectodomain shedding. J Biol. Chem. 272 17160-17165. 

Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM (2005) A diet enriched with the omega-3 fatty add docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosd 25 3032-3040 Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J (2000) Human aspartic protease memapsin 2 cleaves the )-secretase site of P-amyloid precursor protein. Proc Natl Acad Sci USA 97 1456-1460... 

AD plaques are extracellular deposits of aggregated amyloid-P (AP) peptide that is proteolytically derived from the P-amyloid precursor protein (APP). In vitro and in vivo studies have shown that APP abnormalities can affect synaptic vesicle and axonal transport. Axonal dysfunction might lead to impaired synaptic plasticity and reduced neuronal viability. 

Banks, W.A. 2004. The source of cerebral insulin. Eur. J. Pharmacol. 490 5-12 Baiger, S.W. and Mattson, M.P. 1997. Isoform-specific modulation by apohpoprotein E of the activities of secreted P-amyloid precursor protein. J. Neurochem. 69 60-67 Baudier, J. and Cole, R.D. 1987. Phosphorylation of tau proteins to a state like that in Alzheimer s brain is catalyzed by a calcium/calmoduUn-dependent kinase and modulated by phospholipids. J. Biol. Chem. 262 17577-17583... 

Bodies, A.M. and Barger, S.W. 2005. Secreted P-amyloid precursor protein activates microglia via INK and p38-MAPK. NeurobioL Aging 26 9-16 Boulton, T.G., Nye, S.H., Robbins, D.J., Ip, N.Y., Radziejewska, E., Motgenbesser, S.D., De Pinho, R.A., Panayotatos, N., Cobb, M.H. and Yancopoulos, G.D. 1991. ERKs A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65 663-675... 

Gong, C.X., Liu, R, Grundke-Iqbal, I. and Iqbal, K. 2005. Post-translational modifications of tau protein in Alzheimer s disease. J. Neural Transm. 112 813-838 Goodman, Y. and Mattson, M.P. 1994. Secreted forms of P-amyloid precursor protein protect hippocampal neurons against amyloid P-peptide-induced oxidative injury. Exp. Neurol. 128 1-12... 

A. C. and Suzuki, T. 2000. Neuron-specific phosphorylation of Alzheimer s P-amyloid precursor protein by cychn-dependent kinase 5. J. Neurochem. 75 1085-1091... 

Markesbery, W.R. and Lovell, M.A. 1998. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer s disease. Neurobiol. Aging 19 33-36 Marquez-Sterling, N.R., Lo, A.C., Sisodia, S.S. and Koo, E.H. 1997. Trafficking of cell-surface P-amyloid precursor protein Evidence that a sorting intermediate participates in synaptic vesicle recycling. J. Neurosci. 17 140-151... 

Qiu, W.Q., Ferreira, A., Miller, C., Koo, E.H. and Selkoe, D.J. 1995. Cell-surface P-amyloid precursor protein stimulates neurite outgrowth of Mppocampeil neurons in an isoform-dependent manner. J. Neurosci. 15 2157—2167... 

For example, the brains of senescent rats exposed to lead during early development exhibited delayed overexpression of p-amyloid precursor protein (APP) mRNA, altered activities of several signal-dependent and development-specific transcription factors, and elevated concentrations of both APP and the amyloidogenic P-amyloid (AP) product of APP. The effects included a substantial elevation in one of the regulators (Spl) of the APP gene. 

Shaw KT, Utsuki T, Rogers J, Yu QS, Sambamurti K, Brossi A, Ge YW, Lahiri DK, Greig NH (2001) Phenserine regulates translation of P-amyloid precursor protein mRNA by a putative interleukin-1 respraisive element a target Iot drug development. Proc Natl Acad Sci USA 98 7605-7610... 

Fox et al. (2008) reported that in rat retinal rod cells, apoptosis accompanied high Pb exposures in vivo while low exposures induced cell proliferation. There were also decreases in Na" and K -ATPase activity. Wu et al. (2008) probed epigenetic changes in the brains of aging monkeys by using the epigenetic endpoints DNA methyltransferase and mRNA expression of P-amyloid precursor protein, transcription factor Spl. Infancy exposures... 

Aged monkeys tested for DNA methyltransferase, mRNA expression of p-amyloid precursor protein, transcription factor Spl Epigenetic changes in aging brains Infancy PbB levels reported elsewhere Exposure in infancy increased mRNA expression, p-amyloid precursor protein, transcription factor Spl, DNA methyltransferase Wu et al. (2008)... 

Checler F (1995) Processing of the p-amyloid precursor protein and its regulation in alzheimer s disease. J Neurochemistry 65 1431-1444... 

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