Newfound effect of N-acetylaspartate in preventing and reversing aggregation of amyloid-beta in vitro.
Neurobiol Dis
; 117: 161-169, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29859874
ABSTRACT
Although N-acetylaspartate (NAA) has long been recognized as the most abundant amino acid in neurons by far, its primary role has remained a mystery. Based on its unique tertiary structure, we explored the potential of NAA to modulate aggregation of amyloid-beta (Aß) peptide 1-42 via multiple corroborating aggregation assays along with electron microscopy. Thioflavin-T fluorescence assay demonstrated that at physiological concentrations, NAA substantially inhibited the initiation of Aß fibril formation. In addition, NAA added after 25â¯min of Aß aggregation was shown to break up preformed fibrils. Electron microscopy analysis confirmed the absence of mature fibrils following NAA treatment. Furthermore, fluorescence correlation spectroscopy and dynamic light scattering measurements confirmed significant reductions in Aß fibril hydrodynamic radius following treatment with NAA. These results suggest that physiological levels of NAA could play an important role in controlling Aß aggregation in vivo where they are both found in the same neuronal compartments.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Ácido Aspártico
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Agregados Proteicos
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Amiloide
Limite:
Humans
Idioma:
En
Revista:
Neurobiol Dis
Ano de publicação:
2018
Tipo de documento:
Article