J8-Amyloid

Alzheimer s Disease This disease is due to the accumulation of j8-amyloid protein in the brain. The protein is believed to trigger brain degeneration through cell death of the neurons. Alzheimer s disease is characterized by loss of memory and intellectual performance, and slowness in thought. In the United States, a class of drugs called cholinesterase inhibitors is approved to treat Alzheimer s disease. Both Europe and the United States have approved a drug called memantine for treatment of Alzheimer s disease. 

Neuroanatomical and neuropathological basis of Alzheimer s disease Histological features of Alzheimer s disease include neuritic plaques and neurofibrillary tangles (Boiler and Duyckaerts 1997). Neuritic plaques are composed of extracellular deposits of j8-amyloid protein and apolipoprotein E and are found primarily in neocortex. j8-amyloid is derived from an amyloid precursor protein, and is suspected to be a chief causal factor in Alzheimer s disease pathology (Samuel et al. 1997). Neurofibrillary tangles are clusters of protein fibers found in the cell body and composed of tau protein, which normally serves as a cytoskeletal element. Neurofibrillary tangles progress from entorhinal cortex to hippocampus, and then to neocortical areas. 

Gregory DMB, Tammie LS, Burkoth TS, MiUer-Auer H, Lynn DG, Meredith SC, Botto RE. Dipolar recoupUng NMR of biomolecular self-assemblies determining inter- and intrastrand distances in fibrilized Alzheimer s j8-amyloid peptide. Solid State Nucl Magn Reson 1998 13 149 166. 

The RR method has been used to characterize the structures of fragments of amyloid [40, 41]. Griffin et al. [40] have synthesized the j8-amyloid fragment (HzN-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala-COaH) which is the C-ter-minus of the )8-amyloid protein. The structure of this molecule was... 

Fig. 4.9 Processing scheme for the j8-amyloid precursor protein. j8-APP (amyloid precursor protein) is processed in two steps. First, j8-secretase generates two fragments, the j8-amyloid precursor peptide and the C-terminal fragment (CTF-jS) C99. In a second step, the y-secretase cleaves the C99 fragment into an Afl fragment and AlCD (APP Intracellular Domain). Sometimes, y-secretase gen-...

Gorbitz, C.H. The structure of nanotubes formed by diphenylalanine, the core recognition motif of Alzheimer s j8-amyloid polypeptide, ChemComm. 22 (2006) 2332-2334. 

A different kind of relationship between an E2 enzyme and disease is exemplified by the finding that the Alzheimer s amyloid-yS peptide induces the expression of E225K, a mammalian relative of yeast Ubcl [90]. E22sk was found to play a major role in amyloid-j8-dependent neuronal cell killing. This effect may be related... 

Kadlcik V, Sicard-Roselli C, Houee-Levin C, Kodicek M, Ferreri C, Chatgilialoglu C. (2006) Reductive modification of a methionine residue in the amyloid-j8 peptide. Angew Chem IntPd 45 2595-2598. 

Possible conformations for Gly37-Gly38-Val39 were compared of an idealized j8-strand, conformations C (w37-38 = 0°, 38=—121°, 38 = 25°, 39 = -41°, 0)31-3% = 180°) and conformations T ( 37-38 = 180°, < 38 = 0°, i/>38 = -134°, distance constraints indicated that an unusual structure, probably involving a cis amide bond, is present in the aggregated peptide amyloid. This structure is incompatible with the accepted models of fibril structure. 

Maji, S.K., Haidar, D., Drew, M.G.B., Banerjee, A., Das, A.K., Banerjee, A. Self-assembly of j8-tum forming synthetic tripeptides into supramolecular /3-sheets and amyloid-like fibrils in the solid state, Tetrahedron. 60(14) (2004) 3251-3259. 

There are numerous examples of PFG diffusion measurements in studies of CyD complexes. For example, diffusion measurement was used for tracing the interaction between j8-CyD and Alzheimer amyloid yS-peptide [24]. It revealed that... 

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