[HTML][HTML] Prevention of β-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL

YC Shang, ZZ Chong, S Wang, K Maiese - Aging (Albany NY), 2012 - ncbi.nlm.nih.gov
YC Shang, ZZ Chong, S Wang, K Maiese
Aging (Albany NY), 2012ncbi.nlm.nih.gov
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-x L complex and increases the Bcl-x L/Bax complex …
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-x L complex and increases the Bcl-x L/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.
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