Antifibrillizing agents catalyze the formation of unstable intermediate aggregates of beta-amyloid.
Biotechnol Prog
; 26(4): 1172-9, 2010.
Article
en En
| MEDLINE
| ID: mdl-20306540
ABSTRACT
Although Alzheimer's disease (AD) is characterized by the extracellular deposition of fibrillar aggregates of beta-amyloid (Abeta), transient oligomeric species of Abeta are increasingly implicated in the pathogenesis of AD. Natively unfolded monomeric Abeta can misfold and progressively assemble into fibrillar aggregates, following a well-established "on pathway" seeded-nucleation mechanism. Here, we show that three simple saccharides, mannose, sucrose, and raffinose, alter Abeta aggregation kinetics and morphology. The saccharides inhibit formation of Abeta fibrils but promote formation of various oligomeric aggregate species through different "off pathway" aggregation mechanisms at 37 degrees C but not at 60 degrees C. The various oligomeric Abeta aggregates formed when coincubated with the different saccharides are morphologically distinct but all are toxic toward SH-SY5Y human neuroblastoma cells, increasing the level of toxicity and greatly prolonging toxicity compared with Abeta alone. As a wide variety of anti-Abeta aggregation strategies are being actively pursued as potential therapeutics for AD, these studies suggest that care must be taken to ensure that the therapeutic agents also block toxic oligomeric Abeta assembly as well as inhibit fibril formation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Amiloide
Límite:
Humans
Idioma:
En
Revista:
Biotechnol Prog
Asunto de la revista:
BIOTECNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos