Format

Send to

Choose Destination
Neuropharmacology. 2016 Feb;101:309-19. doi: 10.1016/j.neuropharm.2015.09.005. Epub 2015 Sep 8.

The potential of synthetic indolylquinoline derivatives for Aβ aggregation reduction by chemical chaperone activity.

Author information

1
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
2
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.
3
Department of Chemistry, National Taiwan Normal University, Taipei 11677, Taiwan.
4
Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan.
5
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. Electronic address: t43019@ntnu.edu.tw.
6
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. Electronic address: t43006@ntnu.edu.tw.
7
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. Electronic address: hmhsieh@ntnu.edu.tw.

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular β-amyloid (Aβ) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Aβ deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Aβ aggregate reducers could be effective for AD treatment. Using a Trx-His-Aβ biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Aβ aggregation. Treating Tet-On Aβ-GFP 293 cells with these compounds reduced Aβ aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Aβ-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 Aβ-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Aβ-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 Aβ-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment.

KEYWORDS:

Alzheimer's disease; Aβ aggregation; Synthetic indolylquinoline derivatives; Therapeutics

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center