Research Paper Volume 4, Issue 3 pp 187—201
Prevention of β-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL
- 1 Laboratory of Cellular and Molecular Signaling
- 2 Cancer Institute of New Jersey
- 3 New Jersey Health Sciences University, Newark, New Jersey 07101
Received: February 20, 2012 Accepted: March 2, 2012 Published: March 3, 2012https://doi.org/10.18632/aging.100440
How to Cite
Central nervous system microglia promote neuronal regeneration and sequester toxic β-amyloid (Aβ) deposition during Alzheimer's disease. We show that the cytokine erythropoietin (EPO) decreases the toxic effect of Aβ on microgliain vitro. EPO up-regulates the cysteine-rich glycosylated wingless protein Wnt1 and activates the PI 3-K/Akt1/mTOR/ p70S6K pathway. This in turn increases phosphorylation and cytosol trafficking of Bad, reduces the Bad/Bcl-xL complex and increases the Bcl-xL/Bax complex, thus preventing caspase 1 and caspase 3 activation and apoptosis. Our data may foster development of novel strategies to use cytoprotectants such as EPO for Alzheimer's disease and other degenerative disorders.