| Autor: |
Gibson, Gillian, Gunasekera, Nicola, Lee, Maria, Lelyveld, Victor, El-Agnaf, Omar M. A., Wright, Andrew, Austen, Brian |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; 1/15/2004, Vol. 88 Issue 2, p281-290, 10p |
| Abstrakt: |
Familial Danish dementia (FDD) is a rare neurodegenerative disorder, which is pathologically characterized by widespread cerebral amyloid angiopathy, parenchymal protein deposits and neurofibrillary degeneration. FDD is associated with mutation in the BRI gene. In FDD a decamer duplication between codons 265 and 266 in the 3′ region of the BRI gene originates an amyloid peptide named ADan, 11 residues longer than the wild-type peptide produced from the normal BRI gene. ADan deposits have been found widely distributed in the CNS of FDD cases. The deposits of ADan are predominantly non-fibrillar aggregates. We show here that synthetic ADan forms oligomers in vitro , seen by Tricine–PAGE and gel filtration, and higher aggregates, which are seen by atomic force spectroscopy and electron microscopy as carrot-shaped objects that bunch together. Here we report that oligomeric ADan is toxic to neuronal cell lines. We find that the soluble non-fibrillar oligomeric species of both the reduced and oxidized forms of ADan are toxic. These results support the idea that the non-fibrillar soluble aggregates are the pathogenic species, which may play a central role in the pathogenesis of FDD, and imply that similar mechanism may also be involved in other neurodegenerative diseases associated with amyloid deposits. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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