| Autor: |
D S, Yang, L C, Serpell, C M, Yip, J, McLaurin, M A, Chrishti, P, Horne, L, Boudreau, R, Kisilevsky, D, Westaway, P E, Fraser |
| Rok vydání: |
2001 |
| Předmět: |
|
| Zdroj: |
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 8 |
| ISSN: |
1350-6129 |
| Popis: |
Amyloid plaques are the principal features of Alzheimers disease (AD) pathology and are considered to be a major factor in the disease process. These fibrillar deposits are composed primarily of the 40-42 residue amyloid-beta (Abeta) peptide which is a proteolytic product of a larger membrane precursor protein. Electron microscopy and X-ray diffraction have revealed that the mature amyloid fibrils are assembled as a highly beta-sheet polymer that has a well-defined protofilament quaternary structure. This organization is observed for amyloid fibrils from a wide variety of disorders and appears to represent a structural superfamily. Amyloid plaques also contain a number of other components such as proteoglycans that contain highly sulfated glycosaminoglycan (GAG) chains. These amyloid-associated elements may contribute to the aggregation and/or stabilization of Abeta as insoluble fibrils. We have recently developed an aggressive model for Abeta plaque formation in transgenic mice that exhibits an "early-onset" phenotype. Immunocytochemistry has demonstrated that even with this rapid progression, Abeta deposits within the neuropil and cerebrovascular system all co-localize with heparan sulfate proteoglycans (HSPG). These findings indicate a number of structural features that can be targeted as potential sites for the development of amyloid inhibitors. In addition, the use of small compounds that interfere with the proteoglycan-amyloid pathway may be effective therapeutic agents that can be assessed through the use of these transgenic models. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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