Cognitive-performance recovery of Alzheimer's disease model mice by modulation of early soluble amyloidal assemblies.
A rationally designed oligomerization inhibitor interacts with early intermediate assemblies of amyloid-beta polypeptide (Abeta) through the aromatic elements and inhibits their assembly into the toxic oligomers that cause Alzheimer's disease by a unique C(alpha)-methylation beta-breakage strategy. The electrostatic potential of the low-energy conformation of the dipeptide inhibitor bound to Abeta is shown.
Frydman-Marom
Anat
A
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
Rechter
Meirav
M
Shefler
Irit
I
Bram
Yaron
Y
Shalev
Deborah E
DE
Gazit
Ehud
E
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D002460:Cell Line; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005454:Fluorescence Polarization; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D016716:PC12 Cells; D051381:Rats; D055672:Static Electricity
D016229:Amyloid beta-Peptides; D004151:Dipeptides