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

• DOI: 10.1073/pnas.1006091107
• Publication Date: 2010-12-04T06:11:14Z
• Authors: Jung-Suk Choi; Joseph J. Braymer; Ravi P. R. Nanga; Ayyalusamy Ramamo...; Mi Hee Lim
• Keywords: Neurotoxicity; Amyloid (mycology)

The accumulation of metal ions and amyloid-β (Aβ) aggregates found in the brain patients with Alzheimer's disease (AD) has been suggested to be involved AD pathogenesis. To investigate metal-Aβ-associated pathways AD, development chemical tools target metal-Aβ species is desired. Only a few efforts, however, have reported. Here, we report bifunctional small molecules, N-(pyridin-2-ylmethyl)aniline (L2-a) N(1),N(1)-dimethyl-N(4)-(pyridin-2-ylmethyl)benzene-1,4-diamine (L2-b) that can interact both Aβ species, as determined by spectroscopic methods including high-resolution NMR spectroscopy. Using compound L2-b, metal-induced aggregation neurotoxicity were modulated vitro well human neuroblastoma cells. Furthermore, treatment tissue homogenates containing L2-b showed disassembly aggregates. Therefore, our studies presented herein demonstrate value compounds for investigating events their mechanisms pathogenesis potential therapeutics.