Search Results (243)

Alzheimer’s disease (AD) remains an unmet medical challenge, as there are no effective therapies that alter the disease’s progression. While approaches have targeted molecules like acetylcholine (ACh) and glutamate, these strategies have provided only limited benefits and do not address the complex molecular mechanisms underlying AD development. This review suggests that β-alanine (3-aminopropanoic acid) is an underexplored neurotransmitter that could serve as a potential AD drug target. Existing evidence indicates that β-alanine modulates GABAergic and glutamatergic neurotransmission, thereby affecting neuronal hyperexcitability. Additionally, studies suggest that β-alanine has antioxidant effects, reducing oxidative stress caused by reactive oxygen species (ROS). We propose that β-alanine might bind to Aβ/tau proteins, possibly targeting the six-amino acid sequences EVHHQK/DDKKAK, which are involved in protein aggregation. β-Alanine may also influence the release of pro-inflammatory cytokines from microglia, potentially reducing neuroinflammation. We also hypothesize that β-alanine may help regulate metal dyshomeostasis, which leads to ROS production. Taurine, structurally like β-alanine, appears to influence comparable mechanisms. Although structural similarity doesn’t ensure therapeutic effectiveness, this evidence supports considering β-alanine as a treatment for AD. Furthermore, β-alanine and its analogues face challenges, including crossing the blood–brain barrier (BBB) and optimizing structure–activity relationships (SAR). This review includes articles through September 2025, sourced from four databases. Full article

Drought, high temperature, salinity, waterlogging, and nutrient deficiency, along with metal toxicity, are among the environmental factors that have resulted in much alteration of many ecosystems by climate change. Such stresses have dramatically lowered the global average human harvest of core crops, which, in turn, has driven an overall decrease in worldwide agricultural productivity. Plants have developed a variety of defense strategies against biotic and abiotic stress. Evidence of the successful roles of phytohormone-like neurotransmitters in ameliorating the response to stress has already been established. One neurotransmitter accumulated by the plants is gamma-aminobutyric acid (GABA), a non-protein amino acid that is essential for signaling in plant growth regulation and development via the control of physiological and biochemical processes. Plant tissues demonstrate rapid accumulation of GABA when exposed to various abiotic stresses. Consequently, it is imperative to understand how this accumulation affects the resistance and productivity of crops in challenging environmental conditions. Previously, different application methods and doses of GABA on different plant species were used under various abiotic stress conditions. The research findings exhibited that the method and concentration of GABA depend on the type of crop. Furthermore, the GABA dose depends on the methods of GABA application. The present review summarizes the potential doses and methods of applications of GABA under different abiotic stress conditions to ameliorate deficiencies in plant growth, yield, and stress tolerance through the avoidance of oxidative damage and maintenance of cell organelle structures. This review will also describe the complex mechanism by which GABA contributes to the attenuation of the effects of abiotic stresses by regulating some important physiological, molecular, and biochemical processes in crops. Full article

Teleost social behavior plays an important role in foraging, reproduction, and aquaculture management, yet its physiological basis remains poorly understood. This study investigated individual differences in sociability in the large yellow croaker (Larimichthys crocea) using behavioral assays and metabolomic profiling in the brain–intestine axis. Behavioral tests revealed that high-sociability (HS) fish spent significantly more time near conspecifics than low-sociability (LS) fish, indicating clear behavioral divergence between groups. Targeted metabolomics of brain tissue showed distinct neurotransmitter signatures between HS and LS individuals, including significant differences in acetylcholine, DOPAC, xanthurenic acid, and glutamine. Untargeted intestinal metabolomics identified 65 differential metabolites between groups. Intestinal metabolites such as LEA and CEA exhibited significant group-specific variation and were functionally associated with CB1 and CB2 cannabinoid receptors, suggesting a potential endocannabinoid-mediated contribution to sociability differences. Differential metabolites enriched in amino–sugar and nucleotide–sugar metabolic pathways. Integration of behavioral and metabolomic data suggests that neurotransmitter regulation and gut–brain metabolic signaling jointly contribute to sociability differences in large yellow croaker. These findings provide mechanistic insights into social behavior and offer potential biomarkers for welfare assessment and selective breeding in aquaculture. Full article

Gamma-aminobutyric acid (GABA) is a bioactive, non-protein amino acid recognized for its role as an inhibitory neurotransmitter in the human central nervous system. Increasing interest in functional foods has increased attention on GABA due to its potential health benefits, including antihypertensive, anxiolytic, antidepressant, and neuroprotective effects. This review summarizes the natural dietary sources of GABA and explores advanced strategies for enriching dairy products, particularly yogurt and frozen yogurt (froyo), with GABA. Key microbial species capable of GABA biosynthesis via the glutamate decarboxylase (GAD) pathway are discussed, alongside enzymatic production techniques that support controlled GABA synthesis. A major focus of this review is the evaluation of various methods for incorporating GABA into dairy matrices, including direct GABA fortification and in situ fermentation using GABA-producing strains, with comparisons of yield, sensory attributes, and product stability. Physicochemical analyses and sensory evaluations are presented as essential tools for assessing product performance. Furthermore, the review outlines the therapeutic effects of GABA-fortified foods and their potential roles in managing hypertension, stress, and neurodegenerative disorders. Key challenges, including strain-dependent variability in GABA-production, storage stability, and regulatory compliance are addressed, along with market and legislative considerations for GABA-fortified foods. Future perspectives include the development of novel high GABA-producing strains, process optimization to improve product stability and sensory acceptance, and expanded applications within the functional food sector. Overall, this review provides an integrated, up-to-date overview of technological, functional and regulatory aspects, offering a clear scientific foundation for the development and commercialization of GABA-fortified dairy products. Full article

While free amino acids (FAAs) are often regarded as simple building blocks for proteins, various studies show they have more complex roles in the body. This review expands on the FAA’s functions, emphasizing their influence on diverse biological processes. It covers their significance in metabolism, energy production, and the synthesis of neurotransmitters, hormones, and antioxidants. FAAs also serve as signaling molecules that regulate critical pathways related to cell growth, autophagy, and metabolic control. The review highlights their impact on the immune system and their essential roles in gut health, nutrient sensing, and metabolic communication. Drawing on recent findings, we emphasize the importance of measuring FAA levels in biological samples and suggest that their supplementation could be beneficial in clinical nutrition, treating metabolic or immune disorders, and preventing sarcopenia. Overall, FAAs are presented as key signaling agents and biomarkers, with potential for targeting their levels to improve health and treat diseases. Full article

Agmatine is a biogenic amine that functions as a neurotransmitter and exhibits anticonvulsant, antineurotoxic, and antidepressant properties. It can be metabolized into putrescine and urea by canonical agmatinases or by the agmatinase-like protein (ALP), which corresponds to the C-terminal region of the LIMCH1 protein. The amino acid sequence of ALP/LIMCH1 diverges significantly from that of canonical agmatinases and lacks the conserved residues typically required for coordination with Mn²⁺, an essential cofactor for ureohydrolase activity. The three-dimensional structure of ALP/LIMCH1 remains unresolved, and predictive artificial intelligence algorithms such as AlphaFold have failed to model it reliably. As a result, the configuration of its active site and the identity of potential metal-coordinating ligands remain elusive. In this study, we purified recombinant full-length rat LIMCH1 (119.5 kDa) and a truncated ALP variant, ΔLIM-ALP (51 kDa), and analyzed their secondary structures using circular dichroism spectroscopy. Our results indicate that both proteins differ markedly from known ureohydrolases, exhibiting a high proportion of disordered regions (~60%) and β-structures (~30%). In contrast, Escherichia coli agmatinase displays a well-defined α/β/α sandwich fold. Despite these structural differences, ALP/LIMCH1 remain the only known mammalian proteins exhibiting agmatinase activity. To gain insight into the putative active site of ALP, we proposed candidate Mn²⁺-binding residues and generated single-point mutants (N213A, Q215A, D217A, E288A, K290A). Although these mutations did not significantly alter Mn²⁺ binding or its overall content in the protein samples, four mutants exhibited a decreased K_m for agmatine and a reduced V_max when normalized to protein concentration. Full article

Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin–angiotensin system’s counter-regulatory pathway. ACE2 is a multifunctional protein whose location and form determine its catalytic and non-catalytic functions, including amino acid transport, the creation of structural complexes, adhesion, and involvement in signaling pathways. In addition, ACE2 influences neurotransmitter systems in the brain. As the main receptor for SARS-CoV-2, ACE2 has been the subject of increasing research interest. Although ACE2 levels in the brain are low, brain damage from SARS-CoV-2 increases the risk of neurodegenerative diseases. This review aims to clarify an important issue: does the temporary inactivation of ACE2 by the SARS-CoV-2 spike protein play a role in Alzheimer-like neurodegeneration, meaning that the protein may serve as a biomarker or therapeutic target? Full article

Objectives: To investigate the clinical value of cerebrospinal fluid (CSF) testing for biogenic amine, pterins, amino acids, and folates in paediatric onset epilepsies. Methods: Retrospective clinical and biochemical phenotyping of patients with epilepsy who underwent diagnostic CSF measurement of monoamine neurotransmitters, pterins, folates, and amino acids between 2009 and 2022. Results: The studied cohort included 123 patients with epilepsy (mean age at the procedure: 4.54 ± 3.65 years). The diagnostic yield for primary neurotransmitter disorders was 1.68% and zero for inherited amino acid and folate metabolism disorders. Patients with higher seizure frequency showed higher levels of CSF homovanillic acid (HVA) and HVA/5-hydroxyindolacetic acid (5HIAA) ratio. Lower levels of 3-O-methyldopa (3-OMD) were found in patients with co-occurring neurodevelopmental disorders, and lower levels of biopterin, 3-methoxy-4-hydroxyphenylglycol (3-MHPG) and 5-methyltetrahydrofolate (5-MTHF) in those with movement disorders. Significantly lower CSF glutamine levels were found in patients receiving antiseizure medications as polytherapy. Patients with a history of status epilepticus had significantly lower levels of CSF aspartic acid, glycine, leucine, ornithine, and valine, and higher levels of CSF serine. Conclusions: CSF analysis disclosed differences in the concentrations of various metabolites that might be related to the severity of the epilepsy, the presence of comorbid conditions, and medications. Full article

N-chlorotaurine (Tau-Cl) is a mild oxidizing haloamine formed from the reaction of hypochlorous acid (HOCl) with taurine (2-amino-ethanesulfonic acid). It is widely used as a topical antiseptic. In this study, we investigated haloamines derived from the neurotransmitter γ-aminobutyric acid, specifically GABA chloramine and bromamine (GABA-Cl, GABA-Br), as well as their halogenated γ-aminobutyric acid ethyl esters (GABAet-Cl, GABAet-Br). Due to their higher hydrophobicity, the esterified haloamines were more potent oxidants in the presence of lyophilic surfactant micelles, demonstrating their greater ability to access hydrophobic environments. By using fluorescent azapentalenes as molecular targets incorporated into sodium dodecyl sulfate (SDS) micelles, the second-order oxidation rate constants (k₂) resulted in 1.15 × 10² and 1.10 × 10⁴ M⁻¹min⁻¹ for GABA-Cl and GABAet-Cl, respectively. As expected, due to the presence of a bromine atom, GABAet-Br was even more reactive (4.50 × 10⁶ M⁻¹min⁻¹). The ability of GABAet-Br to access hydrophobic sites was demonstrated by comparing the reaction rate using micelles generated by different surfactants such as SDS (4.5 × 10⁶ M⁻¹min⁻¹), cetyltrimethylammonium chloride (CTAC, 2.5 × 10⁴ M⁻¹min⁻¹), and triton X-100 (TX-100, 3.9 × 10³ M⁻¹min⁻¹). GABAet-Cl and GABAet-Br exhibited higher bactericidal activity against Staphylococcus aureus and Escherichia coli, probably due to their increased lipophilicity and improved penetration into microorganisms compared to GABA-Cl and GABA-Br. The enhancement of the oxidation capacity by GABAet-Cl and GABAet-Br represents a new direction in the exploration and application of haloamines as antiseptic agents. Full article

The sustainability of aquaculture is increasingly threatened by rising ocean temperatures occasioned by the continued prevalence of global warming, which can have severe consequences for fish health and productivity. Fish, as ectothermic organisms, are susceptible to temperature fluctuations and prolonged exposure to extreme temperatures can lead to physiological disruptions, including altered metabolic rates, oxidative stress, and immune suppression, ultimately affecting their growth and reproductive success. In response, several strategies, including dietary supplementation, have been proposed to alleviate temperature stress in aquaculture. One such supplement, gamma (γ)-aminobutyric acid (GABA), a non-proteinogenic amino acid, has garnered attention for its potential to enhance stress resilience in aquatic species. In this review, we examine the physiological responses of fish to temperature stress and evaluate the role of GABA in alleviating non-temperature stress. By synthesizing the available evidence, we aim to highlight the potential of GABA as a dietary supplement to improve the resilience of farmed fish to temperature fluctuations, ultimately contributing to sustainable aquaculture in the face of climate change. GABA acts as an inhibitory neurotransmitter in the central nervous system, promoting relaxation and reducing stress. We not only spotlight GABA’s role in the central nervous system, where it has been shown to modulate stress responses by enhancing antioxidant defenses, improving growth performance, and boosting disease resistance, but also emphasize the limited exploration of its potential to mitigate temperature stress in some aquaculture species, particularly economically important fish like olive flounder. Finally, in this review, we provide additional insights into how GABA might help mitigate temperature stress by identifying factors that may influence its supplementation, thereby laying the groundwork for future research on its use as a potential tool for mitigating temperature stress in aquaculture species. Full article

Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision therapy in neonatal seizure syndromes, particularly in pyridoxine-responsive conditions. Methods: We conducted a narrative review of the biochemical functions of vitamin B6, focusing on its active form, pyridoxal 5′-phosphate (PLP), and its role as a coenzyme in neurotransmitter synthesis. We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings. Results: Vitamin B6 is essential for the synthesis of gamma-aminobutyric acid (GABA), dopamine, and serotonin, with PLP-dependent enzymes such as glutamic acid decarboxylase and aromatic L-amino acid decarboxylase playing central roles. Deficiencies in PLP due to genetic mutations or metabolic disruptions can result in treatment-resistant neonatal seizures. Early supplementation, especially in suspected vitamin B6-dependent epilepsies, may provide both diagnostic clarity and seizure control, potentially reducing exposure to conventional antiseizure medications. Conclusions: Vitamin B6-responsive epilepsies highlight the clinical value of mechanism-based, individualized treatment approaches in neonatology. Incorporating genetic and metabolic screening into seizure management may improve outcomes and aligns with the principles of precision medicine. Full article

Gamma-aminobutyric acid (GABA) is a bioactive amino acid with anti-inflammatory and neurotransmitter properties, yet limited information exists regarding its production by Lactiplantibacillus paraplantarum. We evaluated factors that influence GABA synthesis by L. paraplantarum HK-1 and assessed its production in vitro and under simulated gastrointestinal conditions. GABA production was analyzed using HPLC with pre-column derivatization, gene expression was assessed through RT-qPCR, and probiotic characteristics were evaluated using standard microbiological methods. L. paraplantarum HK-1 demonstrated dose-dependent GABA production with monosodium glutamate (MSG) supplementation, achieving maximum levels at 500 mM MSG (161.1 µg/mL), which was significantly higher than those in other treatments (p < 0.01). A strong positive correlation was observed between MSG concentration and GABA production (r = 0.908, p = 0.002). Gene expression analysis revealed a 61.6-fold higher gadB expression at 500 mM MSG compared to 250 mM, though statistical significance with GABA production was not achieved (r = 0.741, p = 0.259). The strain exhibited appropriate probiotic characteristics including γ-hemolytic activity, bile salt tolerance, and acid resistance. Under simulated gastrointestinal conditions, maximum GABA production occurred in the distal colon (148.3 ± 19.0 µg/mL with probiotic vs. 7.2 ± 6.2 µg/mL control), with overall production significantly higher in probiotic-treated groups (p < 0.001). Overall, L. paraplantarum HK-1 produced GABA throughout gastrointestinal phases and showed traits consistent with probiotic use. These results position HK-1 as a promising GABA-producing candidate for functional food applications, pending in vivo validation. Full article

Considering the multiple benefits of nutraceuticals, and given the growing interest in exploring these effects, understanding their mechanisms and implications in mental well-being and neurological integrity is essential and requires further examination to clarify their therapeutic potential. This narrative review provides a comprehensive overview of recent advances in plant-derived nutraceuticals, particularly regarding their impact on mental health and brain function, by examining their bioactive components, their involvement in neuropsychiatric conditions, their role in neurodegeneration, emerging nutraceuticals with clinical relevance, and gut microbiome interactions with nutraceuticals and phytochemicals. Essential fatty acids, prebiotics, phytochemicals, and nutrients such as amino acids, vitamins, minerals, and omega-3 fatty acids contribute to mood regulation and cognitive function. Nutraceuticals can prevent or slow neurodegeneration by targeting misfolded proteins and modulating oxidative stress, neuroinflammation, mitochondrial dysfunction, and dysregulated signaling pathways. Phytochemicals act as phytopsychobiotics, influencing mental health through gut microbiome modulation and generation of bioactive metabolites. Hypericum and curcumin exert neuroprotective, anti-inflammatory, antioxidant, and antidepressant effects. Ginsenosides promote neuroprotection, partially via gut microbiome-mediated mechanisms. Administration of Ginkgo biloba polysaccharides and lavender essential oil improves neurotransmitter regulation, intestinal barrier integrity, and depressive-like behaviors in preclinical models. Omega-3 polyunsaturated fatty acids, anthocyanins, quercetin, catechins, and chlorogenic acid support neuroprotection and cognitive function via modulation of beneficial gut bacteria, short-chain fatty acid production, anti-inflammatory effects, and serotonin metabolism. The landscape of nutraceuticals offers a diverse range of dietary options with considerable potential to promote mental health and prevent neurodegeneration, but further research is required to elucidate how the gut microbiome may enhance these bioactivities. Full article

Patients with mental health disorders often have inadequate intakes of essential amino acids, vitamins, minerals, and fatty acids, which can negatively affect neurotransmitter synthesis, mood, cognitive function, and sensory perception. This study evaluated the nutritional value and sensory acceptability of different flavoured pea protein isolate beverages in 78 patients with schizophrenia spectrum disorders, mood disorders, eating disorders, and depression. The results of the sensory evaluation showed that the sweeter-profile beverages were the best-rated. Nutrient analysis confirmed that the beverages contained important vitamins and minerals, including B₁₂, vitamin C, zinc, and magnesium, as well as tryptophan and alpha-linolenic acid, while being low in saturated fat. The results suggest that pea protein isolate beverages are nutrient-rich, well-tolerated, and sensory-acceptable products with high potential as a complementary nutritional solution in mental healthcare. Full article

Sleep disturbances are linked to metabolic and neurological dysregulation. Moringa oleifera leaves, rich in bioactive compounds, may improve sleep via gut–brain axis modulation. This study investigated the sleep-enhancing effects of fermented Moringa oleifera leaf extract (FM) in mice using metabolomics, gut microbiota analysis, network pharmacology, and molecular docking. A 1:1 combination of Lactobacillus plantarum GDMCC 1.2685 and L. swissii GDMCC 1.791 optimally fermented FM, increasing GABA by 1.67-fold and total amino acids to 46,058.20 ± 845.53 μg/g. FM shortened sleep latency, increased sleep duration, and elevated brain GABA while reducing glutamate (Glu) and Glu/GABA ratios. Hypothalamic metabolomics identified seven sleep-related metabolites, implicating glycerophospholipid, tryptophan, and purine metabolism pathways. FM also reduced Mycobacterium anisopliae (a gut bacterium associated with insomnia) and increased the Firmicutes/Bacteroidetes ratio. Network pharmacology revealed that FM’s effects were mediated via GABA, Glu, and serotonin (5-HT) pathways. These findings demonstrate that FM improves sleep by modulating hypothalamic neurotransmitters and gut microbiota, exerting sedative-hypnotic effects through amino acid, purine, and energy metabolism. Full article