Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid ß-Mediated Neurotoxicity.
Int J Mol Sci
; 16(5): 10526-36, 2015 May 08.
Article
en En
| MEDLINE
| ID: mdl-26006224
ABSTRACT
Alzheimer's disease (AD) is characterized by a large number of amyloid-ß (Aß) deposits in the brain. Therefore, inhibiting Aß aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric Aß-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aß-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of Aß aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated Aß1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aß1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aß fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligosacáridos
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Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Fármacos Neuroprotectores
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Quitosano
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2015
Tipo del documento:
Article
País de afiliación:
China