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

Yan Shang | Zendy; Zhao Zhong Chong | Zendy; Shaohui Wang | Zendy; Kenneth Maiese | Zendy

Open Access

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

Author(s) -

Yan Shang,

Zhao Zhong Chong,

Shaohui Wang,

Kenneth Maiese

Publication year - 2012

Publication title -

aging

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.473

H-Index - 90

ISSN - 1945-4589

DOI - 10.18632/aging.100440

Subject(s) - microglia , erythropoietin , pi3k/akt/mtor pathway , bcl xl , phosphorylation , cytosol , microbiology and biotechnology , apoptosis , neuroprotection , amyloid (mycology) , cancer research , biology , signal transduction , chemistry , programmed cell death , neuroscience , immunology , endocrinology , biochemistry , inflammation , enzyme , botany

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.

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