BROWSE

Related Researcher

Author's Photo

Lim, Mi Hee
MetalloNeuroChemistry Lab (MNCL)
Research Interests
  • Neurodegenerative disease, small molecule design, network between metal, proteins, and ROS

ITEM VIEW & DOWNLOAD

Design of small molecules that target metal-A beta species and regulate metal-induced A beta aggregation and neurotoxicity

Cited 84 times inthomson ciCited 76 times inthomson ci
Title
Design of small molecules that target metal-A beta species and regulate metal-induced A beta aggregation and neurotoxicity
Author
Choi, Jung-SukBraymer, Joseph J.Nanga, Ravi P. R.Ramamoorthy, AyyalusamyLim, Mi Hee
Keywords
Amyloid-β peptide; Copper; Rational structure-based design; Reactive oxygen species; Zinc
Issue Date
2010-12
Publisher
NATL ACAD SCIENCES
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.51, pp.21990 - 21995
Abstract
The accumulation of metal ions and amyloid-β (Aβ) aggregates found in the brain of patients with Alzheimer's disease (AD) has been suggested to be involved in AD pathogenesis. To investigate metal-Aβ-associated pathways in AD, development of chemical tools to target metal-Aβ species is desired. Only a few efforts, however, have been reported. Here, we report bifunctional small molecules, N-(pyridin-2-ylmethyl)aniline (L2-a) and N 1, N 1-dimethyl-N 4-(pyridin-2-ylmethyl)benzene- 1,4-diamine (L2-b) that can interact with both metal ions and Aβ species, as determined by spectroscopic methods including high-resolution NMR spectroscopy. Using the bifunctional compound L2-b, metal-induced Aβ aggregation and neurotoxicity were modulated in vitro as well as in human neuroblastoma cells. Furthermore, treatment of human AD brain tissue homogenates containing metal ions and Aβ species with L2-b showed disassembly of Aβ aggregates. Therefore, our studies presented herein demonstrate the value of bifunctional compounds as chemical tools for investigating metal-Aβ-associated events and their mechanisms in the development and pathogenesis of AD and as potential therapeutics.
URI
Go to Link
DOI
10.1073/pnas.1006091107
ISSN
0027-8424
Appears in Collections:
PHY_Journal Papers
Files in This Item:
2-s2.0-78650669293.pdf Download

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU