High-Throughput Analysis of Alzheimer's beta-Amyloid Aggregation Using a Microfluidic Self-Assembly of Monomersf

Cited 38 time in webofscience Cited 34 time in scopus
  • Hit : 532
  • Download : 9
The principal histopathological feature of Alzheimer's disease is the presence of beta-amyloid (A beta) aggregates in the gray matter of the brain, and researchers believe that various environmental factors play significant roles in the conformational change and self-assembly of A beta peptides. Therefore, discovering a rapid and convenient analytical method of evaluating the environmental factors on A beta aggregation would have a considerable impact. Herein we report our development of a novel microfluidic screening system enabling high-throughput analysis, low-consumption of reagents, and short analytical time. Microchannels with a cross-sectional. dimension of 100 mu m x 100 mu m were immobilized with A beta monomers via N-hydroxysuccinimide ester activation of the internal surfaces, and then a fresh A beta monomer solution mixed with different small molecules or metal ions was continuously introduced into the microchannels to induce A beta aggregation. In this work, we investigated (1) the temporal evolution of A beta aggregation within microchannels, (2) the high-throughput screening of the inhibitory effect of 12 small molecules against A beta aggregation, and (3) the effect of different metal ions (Fe(3+), Cu(2+), Zn(2+), and Al(3+)) on A beta aggregation by using thioflavin T (ThT)-induced fluorescence microscopy and ex situ atomic force microscopy. The microfluidic system should contribute to a simultaneous analysis of multiple environmental factors affecting amyloid aggregates in a parallel manner and to screen therapeutic small molecules prior to their in vivo evaluation.
Publisher
Amer Chemical Soc
Issue Date
2009-04
Language
English
Article Type
Article
Keywords

FIBRILS IN-VITRO; SOLID-SURFACE; PROTEIN AGGREGATION; METAL-IONS; DISEASE; PEPTIDE; NEUROTOXICITY; A-BETA-42; FIBRILLOGENESIS; THERAPEUTICS

Citation

ANALYTICAL CHEMISTRY, v.81, no.7, pp.2751 - 2759

ISSN
0003-2700
DOI
10.1021/ac802701z
URI
http://hdl.handle.net/10203/9432
Appears in Collection
MS-Journal Papers(저널논문)
Files in This Item
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 38 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0