Ser8.5

L-Serine Research

39 peer-reviewed studies · Evidence score: 8.5/10

Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'

Jennings MJ et al. • Journal of neuromuscular diseases (2021)

The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.

The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Further research warranted to confirm findings

Systematic Reviewn=2,046

DOI

NMDA-receptor coagonists in serum, plasma, and cerebrospinal fluid of schizophrenia patients: a meta-analysis of case-control studies

Brouwer A et al. • Neuroscience and biobehavioral reviews (2013)

Blood serine levels were found to be significantly higher in SCZ patients compared to healthy controls (SDM=0.280 (0.021-0.540), p=0.034; N=1671 subjects), whereas CSF serine, l-serine, d-serine, g...

Blood serine levels were found to be significantly higher in SCZ patients compared to healthy controls (SDM=0.280 (0.021-0.540), p=0.034; N=1671 subjects), whereas CSF serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels did not differ.
Stratification by sex suggested that the case-control difference in blood serine levels particularly applies to male subjects.
These results provide support for blood serine level aberrations in SCZ patients and warrant further research to disentangle the involvement of serine with SCZ in both sexes.

Meta-Analysisn=1,671

DOI

Current and Emerging Precision Therapies for Developmental and Epileptic Encephalopathies

Samanta D et al. • Pediatric neurology (2025)

Additionally, the importance of enhancing access to genetic testing, conducting robust natural history studies, and employing innovative clinical trial designs is emphasized.

Additionally, the importance of enhancing access to genetic testing, conducting robust natural history studies, and employing innovative clinical trial designs is emphasized.
Future directions focus on addressing the challenges in developing and implementing gene-based therapies, integrating systems biology, leveraging artificial intelligence for data analysis, and fostering collaboration among stakeholders.
The rapidly advancing field of precision therapeutics for DEEs holds promise to improve outcomes through tailored, equitable, and patient-centered care.

Systematic Review

DOI

Astrocyte-neuron metabolic crosstalk in ischaemic stroke

Ren ZL et al. • Neurochemistry international (2025)

We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the ...

We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the mitochondria.
After IS, astrocytes in the peri-infarct zone can produce lactate, ketone bodies (KBs), glutamine (Gln), and l-serine, shuttling these metabolites, along with mitochondria, to neurons.
This process helps maintain the energy requirements of neurons, preserves their redox state, and regulates neurotransmitter receptor activity.

Systematic Review

DOI

d-amino acids: new functional insights

Pollegioni L et al. • The FEBS journal (2025)

The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Beyond neurotransmission, recent studies have highlighted the versatile roles of d-AAs in cancer, inflammation, immune regulation, kidney disease, and diabetes.
Moreover, these studies suggest that the levels of d-AAs in blood and urine could serve as early biomarkers for conditions such as Alzheimer's disease, schizophrenia, and chronic kidney disease.
Understanding the role of d-AAs in certain pathological states is helping to identify new therapeutic targets, offering promising opportunities for clinical applications in treating various diseases.

Systematic Review

DOI

An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder

Pu J et al. • Molecular psychiatry (2021)

This meta-analysis examined the effects of Acetyl-L-Carnitine.

Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients.
Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.
Further research warranted to confirm findings

Meta-Analysisn=46

DOI

Sources and Sinks of Serine in Nutrition, Health, and Disease

Handzlik MK et al. • Annual review of nutrition (2023)

A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.

Compromised regulation or activity of l-serine synthesis and disposal occurs in the context of genetic diseases as well as chronic disease states, leading to low circulating l-serine levels and pathogenesis in the nervous system, retina, heart, and aging muscle.
Dietary interventions in preclinical models modulate sensory neuropathy, retinopathy, tumor growth, and muscle regeneration.
A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.

Systematic Review

DOI

Astrocyte-neuron metabolic cooperation shapes brain activity

Bonvento G et al. • Cell metabolism (2021)

The paradigm of this biological feature is the astrocyte-neuron couple, in which the glycolytic metabolism of astrocytes contrasts with the mitochondrial oxidative activity of neurons.

The paradigm of this biological feature is the astrocyte-neuron couple, in which the glycolytic metabolism of astrocytes contrasts with the mitochondrial oxidative activity of neurons.
Astrocytes generate abundant mitochondrial reactive oxygen species and shuttle to neurons glycolytically derived metabolites, such as L-lactate and L-serine, which sustain energy needs, conserve redox status, and modulate neurotransmitter-receptor activity.
Conversely, early disruption of this metabolic cooperation may contribute to the initiation or progression of several neurological diseases, thus requiring innovative therapies to preserve brain energetics.

Systematic Review

DOI

Mini review: Lipids in Peripheral Nerve Disorders

Hornemann T • Neuroscience letters (2021)

About 50 % of the brain dry weight consist of lipids, which makes it the second highest lipid rich tissue after adipose tissue.

About 50 % of the brain dry weight consist of lipids, which makes it the second highest lipid rich tissue after adipose tissue.
However, the role of lipids in neurological disorders in particular of the peripheral nerves is not well understood.
This review aims to provide an overview about the role of lipids in the disorders of the PNS.

Systematic Review

DOI

Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases

Lone MA et al. • Advances in experimental medicine and biology (2022)

The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.

While SPTLC1 and SPTLC2 primarily form C18 and C20 LCBs, the combination of SPTLC1 and SPTLC3 produces a broader spectrum of LCBs.
Genetic and population based studies have shown that SPTLC3 expression and function are associated with an altered plasma SL profile and an increased risk for cardio-metabolic diseases.
Animal and in vitro studies showed that SPTLC3 might be involved in hepatic and cardiac pathology and could be a therapeutic target for these conditions.Here we present an overview of the current data on the role of SPTLC3 in normal and pathological conditions.

Systematic Review

DOI

d-serine in physiological and pathological brain aging

Ploux E et al. • Biochimica et biophysica acta. Proteins and proteomics (2021)

NMDAr activation is regulated by many mechanisms.

NMDAr activation is regulated by many mechanisms.
Among is the mandatory binding of a co-agonist, such as the amino acid d-serine, in order to activate NMDAr.
This mini-review presents the most recent information indicating how d-serine could contribute to mechanisms of physiological cognitive aging and also considers the divergent views relative of the role of the NMDAr co-agonist in Alzheimer's disease.Copyright © 2020 Elsevier B.V.

Systematic Review

DOI

L-serine synthesis via the phosphorylated pathway in humans

Murtas G et al. • Cellular and molecular life sciences : CMLS (2020)

We believe that an in-depth investigation of these enzymes is crucial to identify the molecular mechanisms involved in modulating concentrations of the serine enantiomers and for studying the interplay between glial and neuronal cells and also to determine the most suitable therapeutic approach for various diseases.

Indeed, the phosphorylated pathway is strictly linked to cancer.
Moreover, L-serine has been suggested as a ready-to-use treatment, as also recently proposed for Alzheimer's disease.
Here, we present our current state of knowledge concerning the three mammalian enzymes of the phosphorylated pathway and known mutations related to pathological conditions: although the structure of these enzymes has been solved, how enzyme activity is regulated remains largely unknown.

Systematic Review

DOI

NMDA Receptors in Astrocytes

Verkhratsky A et al. • Neurochemical research (2020)

These NMDA receptors generate ionic signals in astrocytes and are linked to several astroglial homoeostatic molecular cascades.

Astroglial cells express an extended complement of ionotropic and metabotropic glutamate receptors, which mediate glutamatergic input to astrocytes.
In particular a sub-population of astrocytes in the cortex and in the spinal cord express specific type of NMDA receptors assembled from two GluN1, one GluN2C or D and one GluN3 subunits.
This composition underlies low Mg2+ sensitivity thus making astroglial NMDA receptors operational at resting membrane potential.

Systematic Review

DOI

D-Amino acids and kidney diseases

Kimura T et al. • Clinical and experimental nephrology (2020)

This new concept, the intra-body dynamics of D-serine, can be useful in the comprehensive management of kidney disease.

Urinary D-serine also reflects other conditions.
The kidney proximal tubule reabsorbs serine with chiral-selectivity, with D-serine being reabsorbed much less efficiently than L-serine, and urinary excretion of D-serine is sensitive to the presence of kidney diseases.
Therefore, assessing the intra-body dynamics of D-serine by measuring its level in blood and urinary excretion can be used to detect kidney diseases and assess pathophysiology.

Systematic Review

DOI

The Neurobiology of d-Serine Signaling

Wolosker H • Advances in pharmacology (San Diego, Calif.) (2018)

Dysfunction of different components of the serine shuttle pathway leads to neurodevelopmental defects, neurodegeneration, and may be involved in psychiatric diseases.

Dysfunction of different components of the serine shuttle pathway leads to neurodevelopmental defects, neurodegeneration, and may be involved in psychiatric diseases.
Serine racemase and other components of the serine shuttle are therefore promising targets for neuroprotective drugs.
Here we review several aspects of the neurobiology of d-serine focusing on mechanisms regulating d-serine signaling in health and disease.

Systematic Review

DOI

Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study

Chester LA et al. • Cannabis and cannabinoid research (2024)

The study was registered on clinicaltrials.gov (NCT05170217).

Discussion: THC induced acute increases in plasma levels of anandamide and noncannabinoid ethanolamides, but there was no evidence that these effects were influenced by the coadministration of CBD.
It is possible that such effects may be evident with higher doses of CBD or after chronic administration.
The progressive reduction in pretreatment anandamide and DEA levels across sessions may be related to repeated exposure to THC or participants becoming less anxious about the testing procedure and requires further investigation.

Crossovern=46

DOI

l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Sasahara I et al. • The Journal of nutrition (2020)

l-Serine and EPA were effective for pain relief in adults with low-back and knee pain after multiplicity adjustment.This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000035056.

l-Serine and EPA were effective for pain relief in adults with low-back and knee pain after multiplicity adjustment.This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000035056.
Further research warranted to confirm findings

RCTn=120

DOI

Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems

Imafuku F et al. • Nutrients (2023)

This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.

All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1).
In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems.
In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements.

RCTn=160

DOI

Potential benefits of l-serine in children with GRIN2B loss-of-function variants: Randomized n-of-1 trials

den Hollander B et al. • Molecular genetics and metabolism (2025)

These pioneering n-of-1 trials provide insights into l-serine's potential for GRIN2B-NDD, with improvements in two of four patients, though no clear distinguishing responder-characteristics were identified.

These pioneering n-of-1 trials provide insights into l-serine's potential for GRIN2B-NDD, with improvements in two of four patients, though no clear distinguishing responder-characteristics were identified.
Future trials should focus on refining patient selection, the use of multiple baseline designs, establishing a core outcome set and pooling treatment data to better understand patient-specific responses.
Further research warranted to confirm findings

RCT

DOI

Effect of a low-volume exercise intervention on the plasma lipidome in people with normal glucose, prediabetes or type 2 diabetes: a randomized controlled trial

Marian OC et al. • American journal of physiology. Endocrinology and metabolism (2025)

This study thus identifies that low-volume exercise can improve novel aspects of the lipidome in metabolic health.

The HIIT + PRT intervention significantly reduced circulating deoxyceramides in the T2D group.
The l-alanine:l-serine ratio positively correlated with deoxyceramide levels, but was unaltered by the HIIT + PRT intervention.
Moreover, excess plasma l-alanine levels may account for the baseline elevated deoxyceramides.

RCTn=74

DOI

Page 1 of 2

View in Research Library