[Abstract Title]. - Society for Neuroscience

neuroprotective effects could arise from interference of Aβ1-42 interactions with α7 nAChRs.
Emerging evidence also indicates that Aβ1-42 can potentiate hyperphosphorylation of tau in cell
lines and in transgenic mice. To further examine the basis of neuroprotective effects, we
evaluated effects in an in vitro model of Aβ1-42-induced tau hyperphosphorylation in
differentiated PC12 cells using in-cell Western blot technique. Exposure of the cells to Aβ1-42
increased phosphorylation of tau at serine-202 and phosphorylation of GSK-3β at tyrosine-216
(GSK-3β-pY216), which were both partially inhibited by the GSK-3ß inhibitor, CHIR98023.
Again, both α7 nAChR selective agonists including A-582941 and PNU-282987, and
antagonists, MLA and α-bungarotoxin partially attenuated the increased phosphorylation tau and
phosphorylation GSK-3β-pY216. This study provide evidence for a role for α7 nAChR
mechanisms underlying Aβ1-42 toxicity, tau phosphorylation and neuroprotection, which, if
translated in vivo, could provide additional basis for their utility of α7 nAChR ligands in
treatment of Alzheimer‟s disease.
Disclosures: M. Hu, None; M.E. Schurdak, None; P.S. Puttfarcken, None; R. El Kouhen,
None; M. Gopalakrishnan, None; J.F. Waring, None; J. Li, None.
Poster
245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 245.17/O11
Topic: C.01.h. Tau
Support: Grant-in-Aid for Matching Fund Subsidy for Private Universities from The Promotion
and Mutual Aid Corporation for Private Schools of Japan
Grant-in-Aid for Scientific Research 11680746 from the Japanese Ministry of
Education, Science, and Culture
Title: Retinoic acid induced activation of GSK3β promoter in neuronal cells
Authors: *O. MURAYAMA, A. SUMIKURA, S. NAKANISHI, Y. SASAKI, M. MATSUDA;
Lab. MolBiol, Sch. Enviro Hlth. Sci., Azabu Univ., Kanagawa, Japan
Abstract: Glycogen synthase kinase 3β (GSK3β) is known as a key protein that involved in
developing Alzheimer‟s disease (AD) via tau phosphorylation. Regulation of GSK3β activity
may be an important target of AD treatment or therapeutics. Previously age dependent increasing
of GSK3β in human brain (Takashima, A. et al. 1998). This suggests that a factor contributing to
GSK3β expression is involved in generating and/or progressing of AD. By using reporter gene