A 3 Amyloid

Harper JD, Wong SS, Lieber CM, Lansbury PT Jr. Assembly of A amyloid protofibrils an in vitro model for a possible early event in Alzheimer s disease. Biochemistry 1999 38 8972-8980. 

Fig. 4. New structural models for amyloid and prion filaments with the parallel and in-register arrangement of //-strands in the //-sheets. //-Strands are denoted by arrows. The filaments are formed by hydrogen-bonded stacks of repetitive units. Axial projections of single repetitive units corresponding to each model are shown on the top. Lateral views of the overall structures are on the bottom. (A) The core of a //-helical model of the //-amyloid protofilament (Petkova et al., 2002). Two such protofilaments coil around one another to form a //-amyloid fibril. (B) The core of a //-helical model of the HET-s prion fibril (Ritter et al., 2005). The repetitive unit consists of two //-helical coils. (C) The core of a superpleated //-structura l model suggested for yeast prion Ure2p protofilaments and other amyloids (Kajava et al., 2004).

Manzamines A, E, F, and Y, 8-hydroxymanzamine A and neo-kauluamine did not show any effect on acetylcholinesterase (AChE) or a-amyloid cleaving enzyme (a-secretase, BACEl) using invitro enzymatic assays. Likewise these compounds did not exhibit any significant ability to protect human neuroblastoma SH-SY5Ycells against oxidative stress-induced cell death [44]. 

It is important to note that effective and good biomarker can be a specific fragment of protein which is present in diseased state but not under normal conditions. Currently, existing biomarker of this type is Ap fragment of a-amyloid protein in Alzheimer s Disease (AD) (Olsson et al., 2003). 

Fig. 12 Comparison of fibril morphology by electron microscopy. A -amyloid peptide (Aj8(io-35)) and B A/3(io-35)-PEG-3OOO conjugate. Scale 200 nm. Reprinted with permission from [53]. Copyright 1998 American Chemical Society...

The structure of transthyretin. The molecule contains eight antiparallel A-strands (A-H) arranged in two parallel planes. The circulating form of transthyretin is a tetramer. Some mutations in the transthyretin gene are associated with amyloidosis and eight of the amino acid alterations causing this disease are indicated. In plasma, transthyretin is a tetramer composed of identical monomers. It appears that mutations cause the monomeric unfolded intermediate of transthyretin to aggregate into an insoluble A-amyloid fibril formation. 

L. Helmuth Further progress on a -amyloid vaccine. Science 289, 375... 

Albumin alpha(l)-acid glycoprotein Albumin lysozyme ribonuclease a Amyloid precursor protein Beta lactoglobulin Botulinum neurotoxin Erythropoietin Erythropoietin Hemoglobin variants, mouse Hemoglobin variants, human Hemoglobin, globin chains HIV-1 reverse transcriptase Insulin trypsin... 

Pentanol is an intermediate in the synthesis of several potential anti-Alzheimer s drugs, which inhibit a-amyloid peptide release and/or its synthesis (33). The enzymatic resolution of racemic 2-pentanol and 2-heptanol by lipase B from Candida antarctica has been demonstrated (34). 

Banerjee, A. Maji, S.K. Drew. M.G.B. Haidar. D. Banerjee. A. Amyloid-like fibril forming antiparallel... 

Pathology series confirm the clinical scarcity of lung disease in AA amyloidosis. Celli et al. (13) reported autopsy findings in seven patients with AA amyloid, none of who had signs or symptoms of lung disease. Amyloid deposits were identified in only three out of seven cases, limited to either lung vessels or airway walls. No interstitial amyloid was detected. An 88-year autopsy experience at Johns Hopkins included 113 cases of A A amyloid, with interstitial disease in one case (14). 

Nichols, M.R., Moss, M.A., Reed, D.K., Lin, W., Mukhopadhyay, R., Hoh, J.H., and Rosenberry, T.L. (2002). Growth of a-amyloid(l lO) protofibrils by monomer elongation and lateral association. Characterization of distinct products by light scattering and atomic force microscopy. Biochemistry 41 6115-6127. 

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