The potential of synthetic indolylquinoline derivatives for Aß aggregation reduction by chemical chaperone activity.
Neuropharmacology
; 101: 309-19, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26362358
ABSTRACT
Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular ß-amyloid (Aß) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Aß deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Aß aggregate reducers could be effective for AD treatment. Using a Trx-His-Aß biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Aß aggregation. Treating Tet-On Aß-GFP 293 cells with these compounds reduced Aß aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Aß-GFP SH-SY5Y cells. Furthermore, treatment with above compounds improved neuronal cell viability, neurite outgrowth, and synaptophysin expression level in mouse hippocampal primary culture under oligomeric Aß-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Aß-induced inhibition of hippocampal long-term potentiation in mouse hippocampal slices. Our results demonstrate how synthetic indolylquinoline compounds are likely to work as chemical chaperones in Aß-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Peptídeos beta-Amiloides
/
Potenciação de Longa Duração
/
Fármacos Neuroprotetores
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Taiwan