Amyloid 3 peptide aggregation

D. It is associated with the deposition of neurotoxic amyloid peptide aggregates. 

Monitoring Alzheimer amyloid peptide aggregation by EPR. Appl Magn Reson 36 209-222... 

Moore, S., Askew, J.A., Gibson, G.L., Aborgrein, A., El-Agnaf, O., Allsop, D., Leung, D.K. and Breslow, R., Novel cyclodextrin dimers and trimers as inhibitors of amyloid peptide aggregation, Neurohiol Aging, 2002, 23, S105. 

The enzymes that are involved in the processing of APP into amyloid peptides are known as secretases. Beta-secretase is an enzyme that catalyzes the initial proteolytic event leading to the production of Abeta amyloid peptides. If APP is cleaved by beta-secretase it can then be further cleaved by gamma-secretase. Abeta peptides are either secreted or intracellularly released. They have varying lengths and represent intermediate degradation products of its precursor (i.e., (3-secretase cleaved APP). Especially the 42 amino acid peptide (A 342) aggregates to form insoluble amyloid plaques. 

Burdick D, Soreghan B, Kwon M, Kosmoski J, Rnauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer s A4/beta amyloid peptide analogs. J Biol Chem 1992 267 546-554. 

Tomski SJ, Murphy RM. Kinetics of aggregation of synthetic beta-amyloid peptide. Arch Biochem Biophys 1992 294 630-638. 

Figure 10-5. Representative conformations of the (5 amyloid peptide (10-42) under different pH conditions. The conformations were obtained as centroids of the most populated clusters from the replica-exchange CPHMD folding simulations [43, 44]. The N-terminal residues 10-28 are shown in blue the C-terminal residues 29-42 are shown in red. In the most aggregation-prone state (pH 6), the side chains of the central hydrophobic cluster Leu-17, Val-18, Phe-19, Phe-20 and Ala-21 are shown as van der Waals spheres in pink, grey, cyan, purple and green, respectively...

Khandogin J, Brooks CL III (2007) Linking folding with aggregation in Alzheimer s beta amyloid peptides. Proc Natl Acad Sci USA 104 16880-16885. 

Wood SJ, Maleeff B, Hart T, Wetzel R (1996) Physical, morphological and functional differences between pH 5.8 and 7.4 aggregates of the Alzheimer s amyloid peptide A. J Mol Biol 256(5) 870-877... 

Figure 17.5. The precursor molecule APP and the three different proteases a, (i, y secretase that are involved in the processing of APPto fS-amyloid peptide. The aberrant processing of the amyloid precursor protein (APP) leads to accumulation of beta-amyloid fragments, first as protofibrils and then as fibers that aggregate in the senile plaque structures. (See color insert.)...

Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T., Jr. (2002). Alpha-synuclein, especially the Parkinson s disease-associated mutants, forms pore-like annular and tubular protofibrils./. Mol. Biol. 322,1089-1102. LeVine, H. (1993). Thioflavine T interaction with synthetic Alzheimer s disease beta-amyloid peptides Detection of amyloid aggregation in solution. Protein Sci. 2, 404—410. Lin, H., Bhatia, R., and Lai, R. (2001). Amyloid beta protein forms ion channels Implications for Alzheimer s disease pathophysiology. FASEB J. 15, 2433-2444. Lorenzo, A., and Yankner, B. A. (1994). Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. USA 91, 12243-12247. Luhrs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Dobeli, H., Schubert, D., and Riek, R. (2005). 3D structure of Alzheimer s amyl o id-( be la) (1—12) fibrils. Proc. Natl. Acad. Sci. USA 102, 17342-17347. 

CD has been used extensively in studies of peptides related to Alzheimers disease, although studies of the amyloid plaques associated with the disease are precluded by their insolubility. 211 A peptide consisting of 39-43 residues is the principal component of amyloid deposits that are found in the brains of Alzheimers patients. This peptide, called A4, 3-peptide, or 3AP for (3-amyloid peptide, is derived by proteolytic cleavage of a protein called amyloid protein (APP). The mechanism of aggregation of (3AP is clearly of great interest. 

Pike, C.J., Walencewicz-Wasserman, A.J., Kosmoski, J., Cribbs, D.H., Glabe, C.G. and Cotman, C.W. (1995) Structure-activity analyses of beta-amyloid peptides contributions of the beta 25-35 region to aggregation and neurotoxicity. J. Neurochem. 64, 253-265. 

Mantyh PW, Ghilardi JR, Rogers S, DeMaster E, Allen CJ, Stimson ER, Maggio JE (1993) Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem 61 1171-1174... 

Esler WP, Stimson ER, Jennings JM, Ghdardi JR, Mantyh PW, Maggio JE (1996) Zinc-induced aggregation of human and rat beta-amyloid peptides in vitro. J Neurochem 66 723-732 Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO (1989) Prevalence of Alzheimer s disease in a community population of older persons. Higher than previously reported. J Am Med Assoc 262 2551-2556 FUss H, Menard M (1992) Oxidant-induced mobilization of zinc from metallothionein. Arch Biochem Biophys 293 195-199... 

Pike CJ, Walencewicz AJ, Glabe CG, Cotman CW (1991) In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res 563 311—314 Prasad AS, Miale A Jr., Farid Z, Sandstead HH, Schulert AR (1963) Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwaifism, and hypognadism. J Lab Qin Med 61 537-549... 

Liu D, Xu Y, Feng Y, Liu H, Shen X, Chen K, Ma J, Jiang H. Inhibitor discovery targeting the intermediate structure of beta-amyloid peptide on the conformational transition pathway implications in the aggregation mechaitism of beta-amyloid peptide. Biochemistry 2006 45 10963-10972. 

LeVine H. Ill Thioflavin-T interaction with syndietic Alzheimers-disease beta amyloid peptides- detection of amyloid aggregation in solution. Protein Sci. 1993 2 404 10. 

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