This approach to improving glutamate transmission is to administer DAAO inhibitors systemically along with small, supplemental doses of D-serine
, in a simple and elegant fashion analogous to the use of Sinemet for the treatment of Parkinson's Disease, as originally conceptualized by Drs.
The researchers used an extensive combination of genetic, pharmacologic and electrophysiological techniques to reveal the role of glutamate receptor-like (GLRs) genes and D-serine in pollen grains, and their physiological impact on plant reproduction.
The new study strongly suggested that D-serine, produced in the female sexual organs might have a role in guiding pollen tubes to their final target.
Serine racemase: a glial enzyme synthesizing D-serine
to regulate glutamate-N-methyl-D-aspartate neurotransmission.
Liquid chromatographic methods for D-serine analysis are divided into 2 types: chiral derivatization with o-phthalaldehyde (CPA) in the presence of chiral thiols such as cysteine analogs, followed by HPLC separation on a nonchiral stationary phase, and nonchiral derivatization with fluorescent reagents followed by HPLC separation with chiral columns (3,14).
We report here a method for measuring D-serine in CSF using 4-(dimethylamino) azobenzene-4'-sulfonyl (dabsyl) chloride labeling and HPLC separation techniques with a simple UV-visible detector.
2 [micro]mol/L) of D-serine and L-serine 5 times on the same day and calculated within-day reproducibility.
Recovery % = (concentration of D-serine + concentration of L-serine calculated after Sumichiral separation)/ (concentration of DL-serine applied to the Sumichiral column from the first RP-18 HPLC run) x 100.
Results have been comparable with D-serine
, another amino acid that has similar receptor activity, and less robust with D-cycloserine, a drug used for tuberculosis, he said.
The Role and Activity of Serine Racemase & D-Serine
We discovered that D-serine, acting in tandem with glutamate, is required for NMDA activation," explained Dr.
This finding suggested that D-serine plays an important regulatory role in the neurotoxic cascade which contributes to cell injury and cell death, and that it accomplishes this by acting as a check on glutamate.
Finding an alternative method of blocking glutamate activation of the NMDA receptor -- by selectively blocking the synthesis of D-serine -- could potentially offer new treatment alternatives for conditions like stroke and chronic degenerative disorders like Parkinson's and Alzheimer's disease," remarked Dr.
Agents that stimulate NMDA receptors should, in theory, benefit those symptom domains, and several substances--glycine, D-serine, and D-cycloserine--are known to cross-react with the site, Dr.
Another amino acid, D-serine, may be most promising of all.