Neuroprotective Approaches for Alzheimer's Disease
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1
University of Groningen, Department of Molecular Neurobiology, Netherlands
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2
Forest Labs, United States
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3
Abbott CNS Drug Discovery, Germany
There is convincing evidence that amyloid-beta 1-42 (Aβ42) in its oligomer conformation is a primary event in the neuropathogenesis of Alzheimer’s disease. The mechanisms of Abeta induced neuropathology, however are only partly known, but observations by us and others point to both inflammation mediated and excitotoxic mechanisms. We will present here data on Aβ42 oligomer- induced neuronal damage and the neuroprotective efficacy of the NMDA antagonist memantine, a calpain inhibitor, and newly developed amyloid modifying peptides both in vitro and in in vivo rodent models. For in vivo testing Aβ oligomers were applied to cholinergic basal forebrain neurons or to the CA1 region of the hippocampus, and the effects of treatments evaluated by cognitive performance measures including novel object recognition and fear conditioning. Both memantine and calpain inhibitor significantly protected against Aβ in a dose dependent manner which was accompanied by an improved cognitive responses. As a more upstream neuroprotective approach in the Aβ cascade, using molecular dynamic methods we developed a new generation of small peptides with anti-amyloid properties. Some promising therapeutic data will be presented based on in vitro and in vivo test experiments.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Oral Presentation
Topic:
Neurodegeneration and neuroprotection
Citation:
Luiten
P,
Nyakas
C,
Masman
M,
Banerjee
P and
Nimmrich
V
(2010). Neuroprotective Approaches for Alzheimer's Disease.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00214
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Received:
04 May 2010;
Published Online:
04 May 2010.
*
Correspondence:
Paul Luiten, University of Groningen, Department of Molecular Neurobiology, Groningen, Netherlands, p.g.m.luiten@rug.nl