Abstract Dr. Wade
Regulation of Serine Racemase Transcription
Deborly Wade, PhD
Abstract
Activated microglia can cause both acute and
delayed neurotoxicity, and most evidence points to a role for excitotoxicity
through hyperstimulation of glutamate receptors. Proinflammatory events in the
brain promote activation of microglia which release ligands for glutamate
receptors, including glutamate itself. However, the receptors related to
excitotoxicity are of the NMDA class which require binding of a second ligand to
a distinct site. Though the traditional agonist of this second site is glycine,
increasing evidence points to an in vivo role for D-serine. D-serine is formed
by a pyridoxal-phosphate dependent enzyme, serine racemase that isomerizes
L-serine to D-serine. Serine racemase is induced in microglia in response to
inflammatory stimuli such as the Alzheimer amyloid -peptide and
lipopolysaccharide. This expression of serine racemase in response to
proinflammatory stimuli suggests a possible mechanism to explain the connections
between inflammation, pain and neurodegeneration. Transcriptional regulation of
serine racemase has not yet been described. The specific aims of this proposal
examine two regulatory regions of serine racemase, the traditional upstream 5’
region, and a potential regulatory region within the first intron.
Updated 10/31/2005
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