Next Article in Journal / Special Issue
β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View
Previous Article in Journal
Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum
Previous Article in Special Issue
5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessFeature PaperArticle
Molecules 2017, 22(10), 1693; doi:10.3390/molecules22101693

Large-Scale Oral Treatment Study with the Four Most Promising D3-Derivatives for the Treatment of Alzheimer’s Disease

1
Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich, Jülich 52425, Germany
2
QPS Austria GmbH, Grambach A-8074, Austria
3
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf 40225, Germany
4
Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4), Forschungszentrum Jülich, Jülich 52425, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 4 September 2017 / Accepted: 4 October 2017 / Published: 10 October 2017
(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)
View Full-Text   |   Download PDF [1014 KB, uploaded 11 October 2017]   |  

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is associated with the aggregation of the amyloid β protein (Aβ). Aβ oligomers are currently thought to be the major neurotoxic agent responsible for disease development and progression. Thus, their elimination is highly desirable for therapy development. Our therapeutic approach aims at specific and direct elimination of toxic Aβ oligomers by stabilizing Aβ monomers in an aggregation-incompetent conformation. We have proven that our lead compound “D3”, an all d-enantiomeric-peptide, specifically eliminates Aβ oligomers in vitro. In vivo, D3 enhances cognition and reduces plaque load in several transgenic AD mouse models. Here, we performed a large-scale oral proof of concept efficacy study, in which we directly compared four of the most promising D3-derivatives in transgenic mice expressing human amyloid precursor protein with Swedish and London mutations (APPSL), transgenic mice, to identify the most effective compound. RD2 and D3D3, both derived from D3 by rational design, were discovered to be the most effective derivatives in improving cognition in the Morris water maze. The performance of RD2- and D3D3-treated mice within the Morris water maze was significantly better than placebo-treated mice and, importantly, nearly as good as those of non-transgenic littermates, suggesting a complete reversal of the cognitive deficit of APPSL mice. View Full-Text
Keywords: Alzheimer’s disease; amyloid β; Aβ oligomers; oral treatment; transgenic mice; d-enantiomeric peptides; large-scale; cognition Alzheimer’s disease; amyloid β; Aβ oligomers; oral treatment; transgenic mice; d-enantiomeric peptides; large-scale; cognition
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kutzsche, J.; Schemmert, S.; Tusche, M.; Neddens, J.; Rabl, R.; Jürgens, D.; Brener, O.; Willuweit, A.; Hutter-Paier, B.; Willbold, D. Large-Scale Oral Treatment Study with the Four Most Promising D3-Derivatives for the Treatment of Alzheimer’s Disease. Molecules 2017, 22, 1693.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top