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

Become EABM
Become Reviewer
Call for Editor


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

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2007
Page: [243 - 251]
Pages: 9
DOI: 10.2174/156720507781077241
Price: $65

Article Metrics

PDF: 12