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Aus der Forschung => Neues aus der Forschung => Topic started by: ama on July 10, 2008, 11:29:34 AM

Title: Alzheimer: Molekül verhindert Bildung von Plaques
Post by: ama on July 10, 2008, 11:29:34 AM

Alzheimer: Molekül verhindert Bildung von Plaques

Cambridge (ddp). Australische Forscher haben mit einem speziellen
Trägermolekül bei Experimenten mit Mäusen typische Symptome von
Alzheimer erfolgreich behandelt. Das Trägermolekül gleicht den Haushalt
bestimmter Metallionen im Gehirn aus und hemmt...


Molekül klaut Alzheimer-Protein die Metalle

Bei den damit behandelten Mäusen reduzierten sich in kurzer Zeit sowohl
die typischen Gehirnschäden als auch die Symptome von Alzheimer, wie Lern-
und Gedächtnisdefizite.


Die originale Quelle:

Cell Press

Copyright  2008 Cell Press. All rights reserved.
Neuron, Vol 59, 43-55, 10 July 2008

Rapid Restoration of Cognition in Alzheimer's Transgenic Mice with
8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial A

Paul A.Adlard,1,2,10 Robert A.Cherny,1,2,5,10 David I.Finkelstein,1,3 ElisabethGautier,5 ElysiaRobb,1 MikhalinaCortes,1
IreneVolitakis,1 XiangLiu,1 Jeffrey P.Smith,1,9 KeylaPerez,1,2 KatrinaLaughton,1,2 Qiao-XinLi,1,2 Susan A.Charman,6 Joseph
A.Nicolazzo,6 SimonWilkins,1,3 KarolinaDeleva,1 ToniLynch,1 GaikKok,5 Craig W.Ritchie,7 Rudolph E.Tanzi,8
 RobertoCappai1,2,4 Colin L.Masters,1,3 Kevin J.Barnham,1,2,4 and Ashley I.Bush1,2,

1 Oxidation Biology Laboratory, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia
2 Department of Pathology, The University of Melbourne, Victoria 3010, Australia
3 Centre for Neuroscience, The University of Melbourne, Victoria 3010, Australia
4 Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
5 Prana Biotechnology Ltd, Parkville, Victoria 3052, Australia
6 Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052, Australia
7 Metabolic and Clinical Trials Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, London
8 Genetics and Aging Research Unit, Massachusetts General Hospital, Building 114, 16th Street, Charlestown, MA 02129, USA

Corresponding author
Ashley I. Bush
abush [bat]

As a disease-modifying approach for Alzheimer's disease (AD), clioquinol
(CQ) targets -amyloid (A) reactions with synaptic Zn and Cu yet promotes
metal uptake. Here we characterize the second-generation 8-hydroxy
quinoline analog PBT2, which also targets metal-induced aggregation of A,
but is more effective as a Zn/Cu ionophore and has greater blood-brain
barrier permeability. Given orally to two types of amyloid-bearing
transgenic mouse models of AD, PBT2 outperformed CQ by markedly decreasing
soluble interstitial brain A within hours and improving cognitive
performance to exceed that of normal littermate controls within days.
Nontransgenic mice were unaffected by PBT2. The current data demonstrate
that ionophore activity, inhibition of in vitro metal-mediated A
reactions, and blood-brain barrier permeability are indices that predict a
potential disease-modifying drug for AD. The speed of recovery of the
animals underscores the acutely reversible nature of the cognitive
deficits associated with transgenic models of AD.

9Present address: Colorado State University-Pueblo, Pueblo, CO 81001, USA
10These authors contributed equally to this work

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Copyright 2007 Elsevier Inc.