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Immusmol's News

11
2024

Amino acids in brain health & disease: why and how to measure them easily ?

Amino Acids in Neurobiology quantification assays ELISA primary antibody

Amino acids are critical for brain function. They serve as building blocks for neurotransmitter and protein synthesis, supply energy, detoxify ammonia, modulate synaptic function, and regulate gene expression. Measuring amino acids and their byproducts in blood, urine, or CSF is therefore critical for assessing neurodegenerative diseases, psychiatric disorders, brain tumors, traumatic injury, stroke, as well as rare neurological diseases.

Over the past 10 years, our team at Immusmol has developed a range of ELISA kits enabling easy quantification of amino acids in research samples. Highly accurate and specific, our ELISA kits have been cross-validated by LC-MS (data available for each kit). In addition, our team has validated a range of primary antibodies for their visualization in cell cultures, tissue sections, and whole mounts.

Here, we provide a quick overview of the role of key amino acids in brain health and disease, and how our tools can help scientists in their detection:

Role in Neurobiology

Nitric Oxide (NO) production: precursor for nitric oxide (NO), a critical neurotransmitter and vasodilatator, influencing cerebral blood flow, synaptic plasticity, learning, and memory

Polyamine synthesis (putrescine, spermidine, spermine): regulating neural growth & differentiation

Brain pathologies

Neurodegenerative diseases: dysregulated NO leads to oxidative stress in Alzheimer’s and Parkinson’s

Stroke: excessive NO exacerbates neuronal damage during ischemia

Urea cycle disorders: elevated levels or metabolic deficiencies in arginine metabolites (Citrullinemia, Ornithine Transcarbamylase Deficiency) lead to hyperammonemia, causing lethargy, seizures, and cognitive impairment

Brain tumors: excess of NO and polyamines often correlates with brain tumor malignancy (angiogenesis, aggressiveness, resistance to therapies)

Research & diagnostics interest

Oxidative stress levels in the context of neurological conditions:  Arginine, Citrulline, Ornithine plasma & CSF levels

Urea cycle disorders: plasma & urine concentrations of citrulline, homoarginine, ornithine

Cerebrovascular risk: arginine & homoarginine plasma levels

Brain tumors: arginine and its metabolites in CSF and plasma

Role in Neurobiology

Protein synthesis: vital for asparagine-linked glycosylation affecting neural proteins

Neurotransmitter regulation: modulates release and synaptic function

Brain pathologies

Asparagine synthetase deficiency: Leads to severe neurodevelopmental delays and epilepsy

Cancer metabolism: Altered levels might affect tumor growth in brain cancers

Research & diagnostics interest

Brain tumor metabolism asparagine levels in plasma or CSF

Neurodegenerative diseases: neurotransmitter amino acid levels in CSF

Associated products
Role in Neurobiology

Primary excitatory neurotransmitter: essential for synaptic transmission.

Synaptic plasticity: crucial for learning and memory formation.

Brain pathologies

Excitotoxicity: Excess leads to neuronal damage in stroke, TBI, ALS, epilepsy.

Mood disorders: altered glutamatergic system in bipolar and major depressive disorders

Brain tumors: secreted by tumors, promoting tumor invasion

Research & diagnostics interest

Stroke, Traumatic brain injury, ALS, Epilepsy: glutamate concentrations in CSF to assess excitotoxic damage.

Mood disorders: glutamate & glutamine levels in serum, CSF and brain tissues

Brain tumors: glutamate concentrations in plasma & CSF

Role in Neurobiology

Glutamate precursor: converted to glutamate in neurons

Glutamine-Glutamate Cycle: shuttles between neurons and astrocytes to maintain glutamate & GABA pools

Brain pathologies

Hepatic Encephalopathy: elevated brain glutamine causes cerebral edema and cognitive impairment

Mood disorders: altered glutamate-glutamine function is associated with depression, anxiety, and schizophrenia

Brain tumor metabolism: glutamine serves as key nutrient, contributing to tumor growth, survival & aggressiveness

Research & diagnostics interest

Hepatic Encephalopathy: detection of high glutamine levels in plasma

Mood disorders: measurement of glutamine, glutamate & GABA in plasma, CSF, and brain tissues

Biomarker of aggressive tumors: glutamine levels in CSF & plasma

Role in Neurobiology

Inhibitory neurotransmitter: glycine mediates inhibitory transmission in the spinal cord and brainstem.

NMDA receptor co-agonist: it binds to NMDA receptors, facilitating excitatory neurotransmission and synaptic plasticity.

Brain pathologies

Glycine encephalopathy (Nonketotic Hyperglycinemia): genetic disorder causing glycine accumulation, leading to seizures, hypotonia, and developmental delay.

Hyperekplexia: mutations in glycine receptors result in exaggerated startle responses and muscle stiffness

Psychiatric disorders: Glycine modulates NMDA receptors, affecting mood, and is a ligand of the newly-discovered metabotropic glycine receptor (mGlyR) involved in stress-induced depression

Brain tumors: aggressive tumors consume and synthesize glycine to proliferate and escape immune control

Research & diagnostics interest

Nonketotic Hyperglycinemia (NKH): measurement CSF and plasma glycine levels

Schizophrenia & mood disorders: glycine CSF and plasma levels can be measured to assess antidepressant effects

Biomarker of aggressive tumor: glycine is marker of high-grade gliomas

Associated products
Role in Neurobiology

Histamine synthesis: precursor to histamine involved in wakefulness, appetite, and cognition.

Myelin sheath formation: supports neuron insulation.

Brain pathologies

Sleep disorders: Altered histamine levels affect sleep cycles (e.g., narcolepsy).

Cognitive dysfunction: histidine deficit in attention deficits and Alzheimer’s.

Brain tumors: glioblastoma stem cells use histidine to produce and secrete histamine to remodel the tumor microenvironment

Research & diagnostics interest

Sleep disorders: histamine levels in CSF

Attention deficit disorders: plasma histidine levels

Brain tumors histidine in CSF & histamine levels in CSF & plasma

Associated products
Role in Neurobiology

Protein synthesis: Essential for proteins production

Epigenetic Regulation: Lysine residues on histones influence gene expression (methylation, acetylation).

Brain pathologies

Lysine deficiency: insufficient levels of Lysine impair neurotransmitter release and cognition.

Glutaric Acidemia Type I: excess of lysine cause neural damage

Brain tumors: glioblastoma stem cells remodel lysine catabolism to repress IFN signaling

Research & diagnostics interest

Insufficiency dietary Lysine uptake: plasma levels of Lysine

Brain tumors: plasma levels & CSF level of Lysine

Associated products

ELISA kit: L-Lysine ELISA

Primary antibody: L-Lysine antibody

Role in Neurobiology

Catecholamine production:  essential for the production of neurotransmitters dopamine, norepinephrine, and epinephrine, influencing motor control, cognition, mood and stress response

Brain pathologies

Phenylketonuria (PKU): L-Phenylalanine accumulation is neurotoxic, disrupting neurotransmitter synthesis and causing neural damage

Tyrosine Hydroxylase Deficiency: causes impaired catecholamine synthesis, leading to motor delays and developmental issues.

Parkinson’s Disease: characterized by dopamine deficiency due to loss of dopaminergic neurons.

Research & diagnostics interest

Dietary Monitoring: phenylalanine levels in plasma

Catecholamines in plasma & CSF: relevant for the assessment and diagnosis of a large array for neurological conditions, such as neuroblastoma, movement disorders, psychiatric diseases, neurodegenerative diseases, cerebrovascular disorders, and drug abuse.

Role in Neurobiology

Protein synthesis: essential for the production of proteins, incorporated into polypeptide chains during translation

Precursor to D-Serine & Glycine: Converted by serine racemase, influencing NMDA receptor activity.

Precursor to Sphingolipids & Phospholipids : essential for myelin sheath formation and neuronal membrane integrity.

Neuroprotection and glial cell proliferation

Brain pathologies

Serine Deficiency Disorders: Leads to severe neurological impairment, including seizures and developmental delays.

Neurodegenerative diseases: L-serine has a neuroprotective activity

Brain tumors:  Serine promotes the survival of glioblastoma cells in hypoxic conditions (one-carbon metabolism)

Research & diagnostics interest

Serine deficiency: plasma levels of L-Serine to assess dietary supplementation

L-Serine imaging to investigate pathogenesis and potential therapeutic strategies in neurodegeneration and neuro-oncology.

Associated products
Role in Neurobiology

Co-agonist at NMDA receptors aiding glutamatergic neurotransmission and synaptic plasticity.

Regulation by astrocytes D-Serine is synthesized and released by astrocytes

Brain pathologies

Schizophrenia: low D-serine levels linked to NMDA receptor hypofunction.

Alzheimer’s Disease: Neurotoxic effects of D-serine metabolism dysregulation (NMDA receptor-mediated excitotoxicity)

ALS: involved in motor neuron degeneration through excitotoxicity

Research & diagnostics interest

Biomarker of Schizophrenia: reduced D-serine serum & CSF levels

Monitoring of therapies targeting NMDA receptors

ALS: D-serine plasma & CSF levels

Associated products
Role in Neurobiology

Protein synthesis: essential for the production of proteins, incorporated into polypeptide chains during translation

Precursor to D-Serine & Glycine: Converted by serine racemase, influencing NMDA receptor activity.

Precursor to Sphingolipids & Phospholipids : essential for myelin sheath formation and neuronal membrane integrity.

Neuroprotection and glial cell proliferation

Brain pathologies

Serine Deficiency Disorders: Leads to severe neurological impairment, including seizures and developmental delays.

Neurodegenerative diseases: L-serine has a neuroprotective activity

Brain tumors:  Serine promotes the survival of glioblastoma cells in hypoxic conditions (one-carbon metabolism)

Research & diagnostics interest

Serine deficiency: plasma levels of L-Serine to assess dietary supplementation

L-Serine imaging to investigate pathogenesis and potential therapeutic strategies in neurodegeneration and neuro-oncology.

Associated products
Role in Neurobiology

Serotonin & melatonin precursor: regulates mood, sleep, and appetite.

Precursor of kynurenines: regulating neuroimmune function, the kynurenine pathway includes neuroprotective kynurenic acid and neurotoxic Quinolinic acid

Brain pathologies

Inflammatory neurological disorders: upregulation of tryptophan catabolism along the kynurenine pathway and reduced serotonin synthesis are observed in depression, anxiety, schizophrenia, neurodegenerative disease, multiple sclerosis, autism, chronic fatigue.

Sleep disorders, Eating Disorders, Migraine, Bipolar disorders involve dysregulated or fluctuating serotonin synthesis

Brain tumors: serotonin promotes glioblastoma growth, migration and angiogenesis. Kynurenine overproduction promote immune tolerance and promote tumor growth (while quinolinic acid exacerbates neural damage)

Research & diagnostics interest

Neuroinflammatory disorders: high kynurenine to tryptophan ratio in plasma & CSF, assessment of concentrations of quinolinic & kynurenic acids, serotonin & melatonin levels

Disorders related to serotonin deficiency / dysregulation: low serotonin levels and 5-HIAA levels in CSF or plasma

Sleep disorders: low melatonin levels in plasma

Brain tumors: Tryptophan to kynurenine ratio and serotonin levels in CSF and plasma, and assessment of Quinolinic acid in CSF


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