Journal Article PreJuSER-12404

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Oral Treatment with the D-Enantiomeric Peptide D3 Improves Pathology and Behavior of Alzheimers disease Transgenic Mice

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2010
Soc. Washington, DC

ACS chemical neuroscience 1, 639 - 648 () [10.1021/cn100057j]

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Abstract: 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.

Keyword(s): J ; Mirror image phage display (auto) ; D-enantiomeric peptide (auto) ; Alzheimer's disease (auto) ; oligomers (auto) ; drugs (auto)


Note: This work has been supported by a grant from Volkswagen-Stiftung to D.W., C.K., and H.S. (I/82 649). Support from the "Prasidentenfond der Helmholtzgemeinschaft" (HGF, "Virtual Institute of Structural Biology") to D.W. is acknowledged. C.M. was supported by a DGCIS grant (French state). The electron microscopy facility used for this work is part of the Partnership for Structural Biology (PSB). Part of this research was supported by P30 NS47466. I.K. and T.v.G have been supported by 5P50 AG16582-10.

Contributing Institute(s):
  1. Strukturbiochemie (ISB-3)
Research Program(s):
  1. Funktion und Dysfunktion des Nervensystems (P33)
  2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2010
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ICS > ICS-6
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