Amyloid P peptides

BACE-1 (p-secretase) is one of the enzymes involved in breaking down APP to produce Ap (amyloid p-peptide, Ap40>42), the protein that eventually oligomerizes to form Ap plaques, the hallmark of Alzheimer s disease (AD). Thus an agent that... 

The sustained attractiveness of photolabeling is apparent from its prominence in studies of y-secretase, an intramembrane protease that contributes to forming amyloid-p peptides and is a major target in Alzheimer s disease [60-62]. y-Secretase is a complex of at least four different polypeptides, and is difficult to engage with high-resolution structural methods. However, in a case of this kind that involves a known target, immunodetection of proteins can often specify the target of y-secretase inhibitor photoaffinity probes such as 19, and proteomic mass spectrometry is not needed. 

Fig. 10.6 Bigenic cluster (apolipoprotein E [APOE + preseirUin 1 [P iD-related serum levels of apolipoprotein E, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, amyloid-P peptide (1 2), and histamine in Alzheimer s disease. (Adapted from refs. 12 9, and 289.)...

Puglielli, L., Ellis, B.C., Saunders, A.J., Kovacs, D.M. (2003) Ceramide stabdizes P-site amyloid precursor protein-cleaving enzyme-1 and promotes amyloid P-peptide biogenesis. /. Biol. Chem., 278, 19777-19783. 

Cole, S.L., Grudzien, A., Manhart, I.O., Kelly, B.L., Oakley, H., Vassar, R. (2005) Statins cause intracellular accumulation of amyloid precursor protein, P-secretase-cleaved fragments, and amyloid P-peptide via an isoprenoid-dependent mechanism. J. Biol. Chem., 280, 18755-18770. 

Kim, W.S., Rahmant, A.S., Kamili, A., et al. (2006) Role of ABCGl and ABCAl in regulation of neuronal cholesterol efflux to apolipoprotein-E discs and suppression of amyloid-P peptide generation. J. Biol. Chem., 282, 2851-2861. 

A similar connection between copper coordination to peptides and medical consequences exists for the Alzheimer disease.79 The amyloid-p peptide in senile plaque is the site of copper binding and as before there is interest to study details of the coordination and the stability. The neurotoxicity seems to be related to free radical damage and Cu2+ chelators are probed as therapy. So far, there seems to be no investigation at a resolution possible to pinpoint copper ligands as derived from ENDOR or related pulse techniques. We mention some relevant EPR studies as introductory sources into the topic.80 81,82... 

Alzheimer s disease0 Amyloid P peptide 40 or 42d Natively unfolded... 

Ruther E., Wiltfang, J. (2004b). Electrophoretic separation of amyloid P peptides in plasma. Electrophoresis 25, 3336-3343. 

Amyloid P peptides in cerebrospinal fluid as profiled with surface enhanced laser desorption/ionization time-of-flight mass spectrometry evidence of novel biomarkers in Alzheimer s disease. 

Compared with AChE in animals such as horse and rat, HA is a weaker inhibitor of human serum BuChE. This selectivity for AChE as opposed to BuChE (similar to that of galanthamine) may suggest a better side-effects profile. However, a stronger inhibition of BuChE could be important in the later stage of AD and could offer more protection over amyloid p-peptide (Ap) plaque deposition. In contrast to isoflurophate, the AChE activity did not decrease with the prolongation of incubation with HA in vitro, and the AChE activity returned to 94% of the control after being washed five times, which indicates a reversible inhibitory action. ... 

Xiao, X. Q. Zhang, H. Y Tang, X. C. Huperzine A attenuates amyloid P-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J. Neurosci. Res., 2002, 67(1) 30-36. 

APP amyloid precursor protein is a single transmembrane molecule, a causative gene of FAD, and is acted upon by proteases to form the amyloid-p peptide. 

T. P. Kaltschmidt et al.,Transcription factor NF-Kappa B is activated in primary neurons by amyloid-P peptides and in neurons surrounding early plaques from patients with Alzheimer s disease, Proc. Natl. Acad. Sci. USA 94 ( 1997) 2642-2647. 

Yamamoto M, Kiyota T, Walsh SM, Ikezu T (2007a) Kinetic analysis of aggregated amyloid-P peptide clearance in adult bone-marrow-derived macrophages from APP and CCL2 transgenic mice. J Neuroimmune Pharm 2 213-227. 

Walter, M.F. Mason, P.E. Mason, R.P. Alzheimer s disease amyloid p peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions. Biochem. Biophys. Res. Commun. 1997, 233, 760-764. 

Recent studies have proposed that beneficial effects of estrogen on AD are directly linked to its ability to reduce amyloid-p peptides and tau aggregates however, despite high expectations, large clinical trials with postmenopausal women indicated that the beneficial effects of estrogen therapies were insignificant and, in fact, elicited adverse effects [463, 464],... 

Wang Q, Yu X, Patal K, Hu R, Chuang S, Zhang G et al (2013) Tanshinones inhibit amyloid aggregation by amyloid-p peptide, disaggregate amyloid fibrils, and protect cultured cells. ACS Chem Neurosci 4 1004-1015... 

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