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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

Yan Chen Shang1,3, Zhao Zhong Chong1,3, Shaohui Wang1,3, Kenneth Maiese1,2,3
  • 1Laboratory of Cellular and Molecular Signaling
  • 2Cancer Institute of New Jersey
  • 3New Jersey Health Sciences University, Newark, New Jersey 07101
Received: February 20, 2012Accepted: March 2, 2012Published: March 3, 2012
https://doi.org/10.18632/aging.100440

Abstract

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.