Oral treatment with the d-enantiomeric peptide D3 improves the pathology and behavior of Alzheimer's Disease transgenic mice.
Several lines of evidence suggest that the amyloid-β-peptide (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Not only Aβ fibrils but also small soluble Aβ oligomers in particular are suspected to be the major toxic species responsible for disease development and progression. The present study reports on in vitro and in vivo properties of the Aβ targeting d-enantiomeric amino acid peptide D3. We show that next to plaque load and inflammation reduction, oral application of the peptide improved the cognitive performance of AD transgenic mice. In addition, we provide in vitro data elucidating the potential mechanism underlying the observed in vivo activity of D3. These data suggest that D3 precipitates toxic Aβ species and converts them into nonamyloidogenic, nonfibrillar, and nontoxic aggregates without increasing the concentration of monomeric Aβ. Thus, D3 exerts an interesting and novel mechanism of action that abolishes toxic Aβ oligomers and thereby supports their decisive role in AD development and progression.
Forschungszentrum Jülich, ISB-3, 52424 Jülich, Germany.
Susanne
S
Aileen Funke
Thomas
T
van Groen
Inga
I
Kadish
Dirk
D
Bartnik
Luitgard
L
Nagel-Steger
Oleksandr
O
Brener
Torsten
T
Sehl
Renu
R
Batra-Safferling
Christine
C
Moriscot
Guy
G
Schoehn
Anselm H C
AH
Horn
Andreas
A
Müller-Schiffmann
Carsten
C
Korth
Heinrich
H
Sticht
Dieter
D
Willbold
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D016896:Treatment Outcome
C534952:D3 peptide; D009842:Oligopeptides