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Kayed/AAAS
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7 T% U4 { ^; ~& H- c8 ]7 ?It was previously thought that the toxicity of A? and other amyloids resulted from large insoluble fibrils, but recently researchers have found that smaller soluble intermediates are cytotoxic. Now, Rakez Kayed, Elizabeth Head, Charles Glabe (University of California, Irvine, CA), and colleagues show that all of the soluble amyloid oligomers tested share a similar structure, and therefore also likely share a common mechanism of pathogenesis.* H3 V0 ]( }! H# a/ r" o! q; o
' y2 T$ Z/ ^% u$ p4 K" U4 G0 t) |Numerous degenerative diseases show evidence of amyloid formation. When the Irvine team raised antibodies against soluble A? oligomers, they obtained a highly specific antibody that binds to antigens based on structure, not amino acid sequence. The antibody binds to A? oligomers, but not to A? monomers or fibrils, or to the natively folded amyloid precursor protein. It also binds strongly and specifically to oligomers formed by numerous other amyloid proteins, including -synuclein, islet amyloid polypeptide, polyglutamine, human insulin, lysozyme, and prion peptide 106–126. Preincubation of the antibody with any of these oligomers blocks their cytotoxicity.9 I6 ~) z$ m9 v' `6 h% M
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"One of the real canons of biochemistry is that structure determines function. So if they all have the same structure, then they must all have a similar function, and all be doing something similar that is bad," says Glabe. Yet, many of the proposed mechanisms make sense for only one of the numerous amyloid diseases, which rules them out in Glabe's view. The real twist, he says, is that about half of the proteins act extracellularly and half intracellularly, leaving pretty much only the plasma membrane as a shared target.1 w, Y* g3 R% _# c$ w
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Reference:2 ~- B3 }- Q) |
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Kayed, R., et al. 2003. Science. 300:486–489.(Preincubation of the antibody with oligo) |
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发表于 2009-3-6 00:43
发表于 2015-6-13 22:17
