Investigating brain <scp>d</scp>‐serine: Advocacy for good practices

Mothet, Jean-Pierre; Billard, J.M.; Pollegioni, Loredano; Coyle, Joseph T.; Sweedler, Jonathan V.

doi:10.1111/apha.13257

Cited by 28 publications

(21 citation statements)

References 94 publications

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“…Thus, the oral ingestion of madecassoside can reduce the production of neuronal D-serine. Although the usage of glutaraldehyde crosslinked antibody has some reservation in case of solid tissues, the cultured-neurons in our experiments have displayed a similar punctate distribution of D-serine in neurons that have been reported earlier 64 .…”

Section: Discussionsupporting

confidence: 79%

Accelerated identification of serine racemase inhibitor from Centella asiatica

Rani

Tyagi

Mazumder

et al. 2020

Sci Rep

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Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over-activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheimer's disease and an effective inhibitor of SR could be a corrective method for the receptor over-activation. We report for the first time here a rapid way of purifying and identifying an inhibitor from medicinal plants known to have the neuro-protective effect. We have purified SR inhibitor from the methanolic extract of Centella asiatica by affinity method. High resolution mass spectrometry and infrared spectroscopy were used to identify the ligand to be madecassoside. We have shown the madecassoside binding in silico and its inhibition of recombinant human serine racemase in vitro and ex vivo. D-serine (DS), an endogenous D-amino acid, is produced by serine racemase (SR) in glial cells and neurons 1 . SR belongs to the class of pyridoxal-5-phosphate (PLP)-dependent enzymes and it converts the free form of L-serine into DS. The free DS functions as a co-agonist of N-methyl-D aspartate (NMDA) receptor in the brain 1 , retina 2 , keratinocytes 3 and in chondrocytes 4 . Incorporation of D-serine causes significant changes in the functional properties of many proteins that are detrimental to humans. Racemization of serine residues is known to occur in beta-amyloid senile plaques of Alzheimer's disease (AD) 5 , human lens protein αcrystallin 6 , human myelin basic protein 7 , osteoarthritic articular and meniscal cartilages 8 , the funnel-web spider toxin 9 , egg ovalbumin 10 and in skin 3 . The conversion of L-serine to D-serine was conclusively established by the discovery of SR in the rat brain by Wolosker et al. in 1999. Active SR is a dimer and needs divalent cations to become functionally active 11 . In addition to serine isomerization, SR also performs α, β-elimination reaction with both L-serine and D-serine to produce pyruvate and ammonia 12 . D-serine is also catabolized by the D-amino acid oxidase (DAAO) 13 . Thus, the D-serine levels are controlled by two enzymes: SR and DAAO.The NMDA receptors are the major ionotropic glutamate receptors in the central nervous system. They control the flow of Ca 2+ ions into the cell, which is essential for the synaptic plasticity, synapse formation, rhythmogenesis, and nerve excitation 14 . One of the main features of the NMDA receptor is that its activation requires simultaneous binding of its agonist glutamate and co-agonist glycine. However, DS also binds to NMDA receptor at the glycine site with three-fold higher affinity than glycine 15 . The efficacy of DS to activate the NMDA receptor is 10 times higher in comparison to glycine 16 . Hyper activation of the NMDA receptor takes place in excess of DS 17 . The hyperactivity of the NMDA receptor is involved in many neurological diseases such as Alzheimer's disease 18,19 amyotrophic lateral sclerosis 20 , epilepsy 21 , neuropa...

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Section: Discussionsupporting

confidence: 79%

Accelerated identification of serine racemase inhibitor from Centella asiatica

Rani

Tyagi

Mazumder

et al. 2020

Sci Rep

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“…Finally, implantable biosensors and surface-scanning biosensors will offer innovative tools for future research aimed at investigating the neurological role of D-AAs, a vibrant field that is growing at an accelerating pace. In past years, considerable progress in understanding D-AAs biology has been made, but the determination of these molecules constitutes a challenging task that can confound observations: we encourage the use of appropriate procedures with multiple controls, as recently suggested by [ 100 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Biosensors for D-Amino Acids: Detection Methods and Applications

Rosini

D’Antona

Pollegioni

2020

IJMS

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D-enantiomers of amino acids (D-AAs) are only present in low amounts in nature, frequently at trace levels, and for this reason, their biological function was undervalued for a long time. In the past 25 years, the improvements in analytical methods, such as gas chromatography, HPLC, and capillary electrophoresis, allowed to detect D-AAs in foodstuffs and biological samples and to attribute them specific biological functions in mammals. These methods are time-consuming, expensive, and not suitable for online application; however, life science investigations and industrial applications require rapid and selective determination of D-AAs, as only biosensors can offer. In the present review, we provide a status update concerning biosensors for detecting and quantifying D-AAs and their applications for safety and quality of foods, human health, and neurological research. The review reports the main challenges in the field, such as selectivity, in order to distinguish the different D-AAs present in a solution, the simultaneous assay of both L- and D-AAs, the production of implantable devices, and surface-scanning biosensors. These innovative tools will push future research aimed at investigating the neurological role of D-AAs, a vibrant field that is growing at an accelerating pace.

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“…While SR catalyses the synthesis of D-serine, both SR and DAAO can mediate its degradation. 1 In ischemia/reperfusion injury (IRI) model in mice, Sasabe et al demonstrated that knock out of SR in mice reduced the basal level of D-serine. However, no alteration of serine enantiomers ratio was observed.…”

Section: D-serine Synthesis and Degradationmentioning

confidence: 99%

“…3 Measurements of D-enantiomers are challenging because they share the same physical properties with the L-enantiomers. 1 Mothet et al emphasized the importance that researchers validate the specificity of their detection through suitable controls. 1 Nowadays, 2D high-performance liquid chromatography (HPLC) is one of the methods of choice for a precise measurement of D-amino acids.…”

mentioning

confidence: 99%

“…It is vital for synapse development and for physiological function of the nervous system. D‐serine was proven to be a ligand for the glycine site of the N‐methyl D‐Aspartate (NMDA) receptor and is synthesized from L‐serine in the brain 1 . As a potent agonist of the receptor, D‐serine is considered to be a potential therapeutic agent in schizophrenia and major depressive disorders, 1 linked to hypo‐function of NMDA receptor‐mediated signalling 2 .…”

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confidence: 99%

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