Abstract | BACKGROUND: RESULTS: We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation. CONCLUSION: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.
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Authors | Thuzar M Shin, J Mario Isas, Chia-Ling Hsieh, Rakez Kayed, Charles G Glabe, Ralf Langen, Jeannie Chen |
Journal | Molecular neurodegeneration
(Mol Neurodegener)
Vol. 3
Pg. 16
(Oct 21 2008)
ISSN: 1750-1326 [Electronic] England |
PMID | 18939994
(Publication Type: Journal Article)
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