Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
Mass Spectrometry Facility, Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):206-210. doi: 10.1080/21678421.2020.1832120. Epub 2020 Oct 14.
D-serine is an endogenous co-agonist with glutamate for activation of the -methyl-D-aspartate receptor (NMDAR). D-serine exacerbates neuronal death and is elevated in the spinal cord from patients with sporadic/familial ALS. The present study was undertaken to examine whether plasma levels of D-serine of patients with ALS are different from those of healthy controls. Levels of D-serine in plasma (30 patients and 30 controls) were measured by high-performance liquid chromatography mass spectrometry. Plasma levels of D-serine in ALS patients (mean 39.27 ± 28.61 ng/ml) were significantly higher ( = 0.0293) than those of healthy control subjects (mean 21.07 ± 14.03 ng/ml) as well as previously reported values for healthy controls; ∼43% of patients had plasma D-serine levels that were 2 to 4-folds higher than those of controls. There was no association of plasma D-serine levels with disability, the duration of disease or with the age of subjects. In conclusion, we show that D-serine levels are elevated in the plasma of some ALS patients. Since D-serine serves as a co-agonist/activator of NMDAR, increases in D-serine could have a direct influence on glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.
D-丝氨酸是一种内源性的谷氨酸共激动剂，可激活 N-甲基-D-天冬氨酸受体（NMDAR）。D-丝氨酸可加重神经元死亡，并在散发/家族性 ALS 患者的脊髓中升高。本研究旨在探讨 ALS 患者的血浆 D-丝氨酸水平是否与健康对照者不同。采用高效液相色谱-质谱法测量了血浆（30 名患者和 30 名对照者）中 D-丝氨酸的水平。ALS 患者的血浆 D-丝氨酸水平（平均值 39.27±28.61ng/ml）明显高于健康对照组（平均值 21.07±14.03ng/ml）（ = 0.0293），也高于之前报道的健康对照组值；约 43%的患者的血浆 D-丝氨酸水平是对照组的 2 至 4 倍。血浆 D-丝氨酸水平与残疾、疾病持续时间或受试者年龄均无相关性。总之，我们表明一些 ALS 患者的血浆 D-丝氨酸水平升高。由于 D-丝氨酸是 NMDAR 的共激动剂/激活剂，D-丝氨酸的增加可能会直接影响谷氨酸能神经传递，并可能导致某些 ALS 患者的兴奋性毒性。
