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Reduction of Aβ42 in brains of transgenic APP swe mice by 2‐3‐chlorophenylaminophenylacetate
Author(s) -
Cohen Margo P,
Shearman Clyde W
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05201.x
Subject(s) - genetically modified mouse , pathogenesis , transgene , amyloid precursor protein , pharmacology , endocrinology , medicine , alzheimer's disease , chemistry , disease , biochemistry , gene
Summary1 Imbalanced generation of the Aβ42 peptide from the amyloid β protein precursor (APP) is implicated in the pathogenesis of Alzheimer's disease. 2 The present study is the first to evaluate the ability of 2‐[3‐chlorophenylamino]phenylacetic acid (GLY‐230), a new drug in clinical development for the treatment of vascular complications of diabetes, to modulate Aβ42 levels in transgenic mice expressing APP. 3 Oral administration of 7.5 mg/kg GLY‐230 twice a day for 14 days to APPswe transgenic mice aged 3 months significantly reduced brain Aβ42 and increased plasma Aβ42 levels by 50 and 20%, respectively. 4 GLY‐230 readily entered the brain after administration of a dose (7.5 mg/kg) that decreased brain Aβ42. 5 These results are the first to demonstrate that GLY‐230, which exhibits antiglycation but no cyclo‐oxygenase inhibitory properties, lowers brain Aβ42 levels in this experimental model of Alzheimer's disease.