Induction of Serine Racemase Expression and D-Serine Release from Microglia by Secreted Amyloid Precursor Protein (sAPP)

Author(s): Shengzhou Wu, Anthony S. Basile, Steven W. Barger.

Journal Name: Current Alzheimer Research

Volume 4 , Issue 3 , 2007

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Abstract:

Alzheimers disease (AD) involves neuronal loss and reduction of synaptic density in specific brain region. Some of the neuronal deaths are associated with excitotoxicity. We previously reported that amyloid β-peptide (Aβ) induced release of N-methyl-D-aspartate receptor (NMDA-R) co-agonists, including glutamate and D-serine. The induction of D-serine production by Aβ involves transcriptional and/or translational regulation of serine racemase gene. Similarly, we report here that conditioned medium from microglia treated with secreted amyloid precursor protein (sAPP) contained elevated levels of D-serine. In microglia, sAPP increased the steady-state dimeric protein level of serine racemase. Promoter- reporter and mRNA analyses suggested that serine racemase is transcriptionally induced by sAPP. These data extend the link between excitotoxicity and neuroinflammation. D-serine may cooperate with glutamate to link neuroinflammation with excitotoxicity, suggesting a pathogenic mechanism applicable to neuronal death in AD and other neurodegenerative diseases.

Keywords: Luciferase Reporter Assay, neuroprotection, inflammation, NMDA receptors, beta-amyloid precursor protein

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2007
Page: [243 - 251]
Pages: 9
DOI: 10.2174/156720507781077241
Price: $58

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