Microfluidic dissociation and clearance of Alzheimer's beta-amyloid aggregates.
The abnormal aggregation of beta-amyloid peptide (Abeta) in the brain is a major histopathological feature of Alzheimer's disease. Herein, we first report on microfluidic dissociation and clearance analysis of pre-formed Abeta aggregates for parallel screening of aggregate destabilizers. As a proof of the concept for the microfluidic platform, we investigated (1) microfluidics-based clearance of metal ion-induced Abeta aggregates using different types of metal chelators, (2) the clearance effect of deferoxamine on Abeta aggregates within microchannels, (3) comparison between destabilized Abeta dissociated from pre-formed Abeta aggregates and remaining deposits within the microchannels both before and after the clearance, and (4) secondary structure change in Abeta deposits by the clearance treatment. The microfluidics-based clearance system should be suitable for efficient screening of chemical candidates to enhance the clearance of Abeta deposits prior to their in vivo evaluation.
Lee
Joon Seok
JS
Institute for the BioCentury and Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 335 Science Road, Daejeon 305 701, Republic of Korea.
Park
Chan Beum
CB
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D003676:Deferoxamine / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D044085:Microfluidics / Q000379:methods*; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D007502:Iron Chelating Agents; D012996:Solutions; D007501:Iron; D003676:Deferoxamine