Selection of peptides binding to the amyloid b-protein reveals potential inhibitors of amyloid formation.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaques, cerebrovascular amyloid deposits, intracellular neurofibrillary tangles, and neuronal loss. Amyloid deposits are composed of insoluble fibers of a 39-43 amino acid peptide named the amyloid beta-protein (A beta). Neuropathological and genetic studies provide strong evidence of a key role for A beta amyloidosis in the pathogenesis of AD. Therefore, an obvious pharmacological target for treatment of AD is the inhibition of amyloid growth and/or inhibition of amyloid function. We took an unbiased approach to generate new inhibitors of amyloid formation by screening a FliTrx combinatorial peptide library for A beta binding peptides and identified four groups of peptides with different A beta binding motifs. In addition, we designed and examined peptides mimicking the A beta binding domain of transthyretin (TTR). Our results showed that A beta binding peptides selected from FliTrx peptide library and from TTR-peptide analogs are capable of inhibiting A beta aggregation and A beta deposition in vitro. These properties demonstrate that binding of selected peptides to the amyloid beta-protein may provide potent therapeutic compounds for the treatment AD.
Schwarzman
Alexander L
AL
Institute for Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Tsiper
Maria
M
Gregori
Luisa
L
Goldgaber
Dmitry
D
Frakowiak
Janusz
J
Mazur-Kolecka
Bozena
B
Taraskina
Anastasia
A
Pchelina
Sofia
S
Vitek
Michael P
MP
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D019151:Peptide Library; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D009842:Oligopeptides; D019151:Peptide Library; D011228:Prealbumin