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J Biol Chem, Vol. 274, Issue 36, 25945-25952, September 3, 1999
From the Alzheimer's disease is characterized by
extensive cerebral amyloid deposition. Amyloid deposits associated with
damaged neuropil and blood vessels contain abundant fibrils formed by
the amyloid
Amyloid
-Protein Fibrillogenesis
STRUCTURE AND BIOLOGICAL ACTIVITY OF PROTOFIBRILLAR
INTERMEDIATES
,,,,§,, and
Center for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts
02115 and the § Department of Physics and Center for
Material Science and Engineering, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
-protein (A). Fibrils, both in vitro and
in vivo, are neurotoxic. For this reason, substantial
effort has been expended to develop therapeutic approaches to control
A production and amyloidogenesis. Achievement of the latter goal is
facilitated by a rigorous mechanistic understanding of the
fibrillogenesis process. Recently, we discovered a novel intermediate
in the pathway of A fibril formation, the amyloid protofibril
(Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., and Teplow, D. B. (1997) J. Biol. Chem. 272, 22364-22372). We report here results of studies of the assembly,
structure, and biological activity of these polymers. We find that
protofibrils: 1) are in equilibrium with low molecular weight A
(monomeric or dimeric); 2) have a secondary structure characteristic of
amyloid fibrils; 3) appear as beaded chains in rotary shadowed
preparations examined electron microscopically; 4) give rise to mature
amyloid-like fibrils; and 5) affect the normal metabolism of cultured
neurons. The implications of these results for the development of
therapies for Alzheimer's disease and for our understanding of fibril
assembly are discussed.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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|
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|
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|
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|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
C. Valery, F. Artzner, B. Robert, T. Gulick, G. Keller, C. Grabielle-Madelmont, M.-L. Torres, R. Cherif-Cheikh, and M. Paternostre Self-Association Process of a Peptide in Solution: From {beta}-Sheet Filaments to Large Embedded Nanotubes Biophys. J., April 1, 2004; 86(4): 2484 - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
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