Title: Dose-dependent improvements in learning and memory deficits in APPPS1-21 transgenic mice treated with the orally active Aβ toxicity inhibitor SEN1500
Authors: Lo, Adrian ×
Tesseur, Ina
Scopes, David I C
Nerou, Edmund
Callaerts-Vegh, Zsuzsanna
Vermaercke, Ben
Treherne, J Mark
De Strooper, Bart
D'Hooge, Rudi #
Issue Date: Dec-2013
Publisher: Elsevier Ltd.
Series Title: Neuropharmacology vol:75 pages:458-466
Article number: S0028-3908(13)00397-3
Abstract: In the Alzheimer's disease (AD) brain, accumulation of Aβ1-42 peptides is suggested to initiate a cascade of pathological events. To date, no treatments are available that can reverse or delay AD-related symptoms in patients. In the current study, we introduce a new Aβ toxicity inhibitor, SEN1500, which in addition to its block effect on Aβ1-42 toxicity in synaptophysin assays, can be administered orally and cross the blood-brain barrier without adverse effects in mice. In a different set of animals, APPPS1-21 mice were fed with three different doses of SEN1500 (1 mg/kg, 5 mg/kg and 20 mg/kg) for a period of 5 months. Cognition was assessed in a variety of behavioral tests (Morris water maze, social recognition, conditioned taste aversion and passive avoidance). Results suggest a positive effect on cognition with 20 mg/kg SEN1500 compared to control APPPS1-21 mice. However, no changes in soluble or insoluble Aβ1-40 and Aβ1-42 were detected in the brains of SEN1500-fed mice. SEN1500 also attenuated the effect of Aβ1-42 on synaptophysin levels in mouse cortical neurons, which indicated that the compound blocked the synaptic toxicity of Aβ1-42. In vitro and in vivo effects presented here suggest that SEN1500 could be an interesting AD therapeutic.
ISSN: 0028-3908
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
× corresponding author
# (joint) last author

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