Inhibition of Abeta42 aggregation using peptides selected from combinatorial libraries.
Increasing evidence suggests that the aggregation of the small peptide Abeta42 plays an important role in the development of Alzheimer's disease. Inhibiting the initial aggregation of Abeta42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Abeta42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Abeta42 fibers.
Baine
Michael
M
Department of Chemistry and Biochemistry, Loyola Marymount University, One LMU Drive, Los Angeles, CA 90045, USA.
Georgie
Daniel S
DS
Shiferraw
Elelta Z
EZ
Nguyen
Theresa P T
TP
Nogaj
Luiza A
LA
Moffet
David A
DA
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D052160:Benzothiazoles; D004353:Drug Evaluation, Preclinical; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D019151:Peptide Library; D010455:Peptides; D013844:Thiazoles; C009462:thioflavin T