[Abstract Title]. - Society for Neuroscience

Poster
244. Abeta Toxicity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 244.17/M10
Topic: C.01.c. Abeta toxicity
Support: FONDECYT 1080221
Title: The inhibition of c-Abl/p73 signal pathway ameliorate neurologic damage in a
Alzheimer‟s disease transgenic mouse model
Authors: *G. I. CANCINO 1 , A. R. ALVAREZ 2 ;
1 Facultad Ciencias Biologicas, P. Univ. Catolica Chile, Santiago, Chile; 2 Dep Biologia Celular y
Mol., P. Univ. Catolica de Chile, Santiago, Chile
Abstract: Alzheimer‟s disease (AD) is characterized by the presence of neurofibrillary tangles
and senile plaques formed by amyloid β-peptide (Aβ). Aβ induces neuronal dystrophy, neuronal
dysfunction and apoptosis. Nevertheless, the mechanisms by which the neurons degenerate are
unknown. In previous in vitro and in vivo studies, we demonstrated that Aβ as fibrils activate the
c-Abl/p73 pathway. Here, we analyzed the role of the c-Abl/p73 pathway in an AD double
transgenic animal model, the APPswe/PSEN1ΓΔ9 mouse. Immunohistochemistry analysis
showed that p73 and tau were phosphorylated and caspase-3 was activated in double transgenic
mouse. Moreover, STI571, a c-Abl kinase inhibitor, significantly prevented its phenomenon.
This inhibitor also reduced the spatial learning impairments, evaluated by Morris Water Maze
task. The transgenic mice treated with intraperitoneal injection of STI571 presents significantly
lower escape latency values and better navigation pattern than the transgenic mice treated with a
saline solution indicating that STI571 treatment is able to reduce the cognitive impairments on
spatial memory performance presents in the transgenic mice. Therefore inhibition of the c-
Abl/p73 pathway may be an alternative for AD therapeutic design.
This work was supported by FONDECYT 1080221
Disclosures: G.I. Cancino , None; A.R. Alvarez, None.
Poster
244. Abeta Toxicity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm