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[P‐185]: Estrogen receptor beta selective ligands for prevention of neurodegeneration: From in silico screening to at bench bioanalysis
Author(s) -
Zhao Liqin,
Diaz Brinton Roberta
Publication year - 2005
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2005.06.380
Subject(s) - virtual screening , estrogen receptor , neurodegeneration , in silico , estrogen receptor beta , estrogen receptor alpha , estrogen , small molecule , selective estrogen receptor modulator , neuroprotection , chemistry , drug discovery , biology , pharmacology , biochemistry , medicine , disease , endocrinology , gene , genetics , cancer , breast cancer
of A 12-28P in AD Tg model mice. Methods: Female APP/ PS1 Tg AD mice were treated with A 12-28P (1mg of peptide or placebo administered intraperitoneally) for five months starting from the age of two months, which is prior to the onset of detectable brain amyloid deposits. Conclusions: Treatment with A 12-28P resulted in a significant reduction of A load: 51.6% in the neocortex, 40.0% in the hippocampus, and 49.2% in the cingulate/retropslenial cortex (p 0.01). Fibrillar A , detected by Thioflavin-S staining, was reduced by 21.9%, 24.7%, and 28.9%, respectively (p 0.05). Levels of formic acid extracted A 1-40 and A 1-42 were decreased on ELISA measurements by 42.5% and 29.9%, respectively (p 0.01). No signs of toxicity or any autoimmune reaction were observed in treated animals. These results demonstrate that pharmacological blocking of the apoE/A interaction may be used to prevent A deposition in AD patients.