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Search Results (298)

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Keywords = gamma−aminobutyric acid (GABA)

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35 pages, 2638 KiB  
Review
Genetic Divergence and Functional Significance of Bioactive Compounds in Rice and Barley: Implications for Biofortification and Human Health
by Essam ElShamey, Jiazhen Yang, Xiaomeng Yang, Md. Mahmudul Hasan, Tao Yang and Yawen Zeng
Int. J. Mol. Sci. 2025, 26(15), 7374; https://doi.org/10.3390/ijms26157374 - 30 Jul 2025
Viewed by 156
Abstract
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) [...] Read more.
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) and barley (Hordeum vulgare) are key dietary staples with distinct genetic architectures influencing the biosynthesis and accumulation of these bioactive compounds. In this study, we explore the interaction and divergence of gene loci associated with GABA, RS, and alkaloid pathways in rice and barley, leveraging comparative genomics to identify conserved and species-specific regulatory mechanisms. We highlight key quantitative trait loci (QTLs) and candidate genes, such as GAD (glutamate decarboxylase) for GABA synthesis, SSIIa and GBSS for RS formation, and alkaloid biosynthesis genes including CYP80G2. Additionally, we discuss the health implications of these functional components, including their roles in reducing hypertension, managing diabetes, and exhibiting neuroprotective effects. Understanding the genetic differences between rice and barley in accumulating these compounds can guide biofortification strategies to enhance nutritional quality in cereal crops, ultimately benefiting human health and dietary outcomes. Full article
(This article belongs to the Special Issue Molecular Insight into Plant Bioactive Compounds)
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30 pages, 2595 KiB  
Review
Gut–Brain Axis in Mood Disorders: A Narrative Review of Neurobiological Insights and Probiotic Interventions
by Gilberto Uriel Rosas-Sánchez, León Jesús Germán-Ponciano, Abraham Puga-Olguín, Mario Eduardo Flores Soto, Angélica Yanet Nápoles Medina, José Luis Muñoz-Carillo, Juan Francisco Rodríguez-Landa and César Soria-Fregozo
Biomedicines 2025, 13(8), 1831; https://doi.org/10.3390/biomedicines13081831 - 26 Jul 2025
Viewed by 948
Abstract
The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood [...] Read more.
The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood regulation and the treatment of anxiety and depression disorders. The findings indicate that several probiotic strains, such as Lactobacillus and Bifidobacterium, have demonstrated anxiolytic and antidepressant effects in pre and clinical studies. These effects seem to be mediated by the regulation of the hypothalamic–pituitary–adrenal axis (HPA), the synthesis of neurotransmitters such as serotonin (5-HT) and Gamma-amino-butyric acid (GABA), as well as the modulation of systemic inflammation. However, the lack of standardization in dosing and strain selection, in addition to the scarcity of large-scale clinical studies, limit the applicability of these findings in clinical therapy. Additional research is required to establish standardized therapeutic protocols and better understand the role of probiotics in mental health. The aim of this narrative review is to discuss the relationship between the gut microbiota and the MGB axis in the context of anxiety and depression disorders, the underlying neurobiological mechanisms, as well as the preclinical evidence for the effect of probiotics in modulating these disorders. In this way, an exhaustive search was carried out in scientific databases including PubMed, ScienceDirect, Scopus, and Web of Science. Preclinical research evaluating the effects of different probiotic strains in animal models during chronic treatment was selected, excluding those studies that did not provide access to the full text. Full article
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20 pages, 2062 KiB  
Review
Neuroplasticity-Based Approaches to Sensory Processing Alterations in Autism Spectrum Disorder
by Maria Suprunowicz, Julia Bogucka, Natalia Szczerbińska, Stefan Modzelewski, Aleksandra Julia Oracz, Beata Konarzewska and Napoleon Waszkiewicz
Int. J. Mol. Sci. 2025, 26(15), 7102; https://doi.org/10.3390/ijms26157102 - 23 Jul 2025
Viewed by 378
Abstract
Sensory dysregulation represents a core challenge in autism spectrum disorder (ASD), affecting perception, behavior, and adaptive functioning. The brain’s ability to reorganize, known as neuroplasticity, serves as the basic principle for therapeutic interventions targeting these deficits. Neuroanatomical mechanisms include altered connectivity in the [...] Read more.
Sensory dysregulation represents a core challenge in autism spectrum disorder (ASD), affecting perception, behavior, and adaptive functioning. The brain’s ability to reorganize, known as neuroplasticity, serves as the basic principle for therapeutic interventions targeting these deficits. Neuroanatomical mechanisms include altered connectivity in the sensory and visual cortices, as well as in the limbic system and amygdala, while imbalances of neurotransmitters, in particular glutamate and gamma-aminobutyric acid (GABA), contribute to atypical sensory processing. Traditional therapies used in sensory integration are based on the principles of neuroplasticity. Increasingly, new treatments use this knowledge, and modern therapies such as neurofeedback, transcranial stimulation, and immersive virtual environments are promising in modulating neuronal circuits. However, further research is needed to optimize interventions and confirm long-term effectiveness. This review discusses the role of neuroplasticity in the etiopathogenesis of sensory integration deficits in autism spectrum disorder. The neuroanatomical and neurotransmitter basis of impaired perception of sensory stimuli is considered, and traditional and recent therapies for sensory integration are discussed. Full article
(This article belongs to the Special Issue Molecular Investigations in Neurodevelopmental Disorders)
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27 pages, 1897 KiB  
Article
A Proton Magnetic Resonance Spectroscopy (1H MRS) Pilot Study Revealing Altered Glutamatergic and Gamma-Aminobutyric Acid (GABA)ergic Neurotransmission in Social Anxiety Disorder (SAD)
by Sonja Elsaid, Ruoyu Wang, Stefan Kloiber, Kimberly L. Desmond and Bernard Le Foll
Int. J. Mol. Sci. 2025, 26(14), 6915; https://doi.org/10.3390/ijms26146915 - 18 Jul 2025
Viewed by 399
Abstract
Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + [...] Read more.
Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article
(This article belongs to the Section Molecular Neurobiology)
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14 pages, 1091 KiB  
Review
Gamma-Aminobutyric Acid: A Novel Biomolecule to Improve Plant Resistance and Fruit Quality
by Jingrong Wang, Shaokun Sun, Wei Fang, Xin Fu, Fuguo Cao and Shujun Liu
Plants 2025, 14(14), 2162; https://doi.org/10.3390/plants14142162 - 13 Jul 2025
Viewed by 513
Abstract
Gamma-aminobutyric acid (GABA), a ubiquitous non-protein amino acid, plays a vital role in the response of plants to biotic and abiotic stresses. This review summarizes the underlying mechanisms through which GABA contributes to plant stress resistance, including its biosynthetic and metabolic pathways, as [...] Read more.
Gamma-aminobutyric acid (GABA), a ubiquitous non-protein amino acid, plays a vital role in the response of plants to biotic and abiotic stresses. This review summarizes the underlying mechanisms through which GABA contributes to plant stress resistance, including its biosynthetic and metabolic pathways, as well as its regulatory roles in enhancing stress tolerance and improving fruit quality. In plants, GABA is primarily synthesized from glutamate by the enzyme glutamate decarboxylase (GAD) and further metabolized by GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). The accumulation of GABA regulates various physiological and biochemical processes, including the control of stomatal closure, enhancement of antioxidant capacity, maintenance of ionic homeostasis, and stabilization of cellular pH. Moreover, GABA interacts with phytohormones to regulate plant growth, development, and stress tolerance. Notably, increasing GAD expression through genetic engineering has been shown to enhance tolerance to stresses, such as drought, saline-alkali, cold, and heat, in various plants, including tomato, rice, and creeping bentgrass. Additionally, GABA has effectively improved the storage quality of various fruits, including citrus fruits, apples, and strawberries. In conclusion, GABA holds significant research potential and promising applications in agricultural production and plant science. Full article
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17 pages, 811 KiB  
Article
A Novel GABA-Producing Levilactobacillus brevis Strain Isolated from Organic Tomato as a Promising Probiotic
by Asia Pizzi, Carola Parolin, Davide Gottardi, Arianna Ricci, Giuseppina Paola Parpinello, Rosalba Lanciotti, Francesca Patrignani and Beatrice Vitali
Biomolecules 2025, 15(7), 979; https://doi.org/10.3390/biom15070979 - 8 Jul 2025
Viewed by 538
Abstract
Gamma-aminobutyric acid (GABA) is a non-protein amino acid playing a significant role in the central nervous system and the gut–brain axis. This study investigated the potential to produce GABA by lactic acid bacteria (LAB) isolated from different varieties of organic tomatoes. The isolated [...] Read more.
Gamma-aminobutyric acid (GABA) is a non-protein amino acid playing a significant role in the central nervous system and the gut–brain axis. This study investigated the potential to produce GABA by lactic acid bacteria (LAB) isolated from different varieties of organic tomatoes. The isolated LAB were taxonomically identified by 16S rRNA gene sequencing, the presence of the gadB gene (glutamate decarboxylase) was detected, and GABA production was quantified using HPLC. Levilactobacillus brevis CRAI showed the highest GABA production under optimised fermentation conditions with 4% monosodium glutamate (MSG). The genome sequencing of L. brevis CRAI revealed the presence of gadA and gadB isoforms and assessed the strain’s safety profile. The gene expression analysis revealed that the gadA and gadB genes were upregulated in the presence of 4% MSG. The probiotic potential of L. brevis CRAI was also assessed by functional assays. The strain showed strong antimicrobial activity against representative enteropathogens, i.e., Escherichia coli ETEC, Salmonella choleraesuis, and Yersinia enterocolitica, and anti-inflammatory effect, reducing nitric oxide production in LPS-stimulated RAW264.7 macrophages. In addition, its ability to adhere to intestinal epithelial Caco-2 cells was demonstrated. These results highlight L. brevis CRAI as a promising candidate for the development of GABA-enriched functional foods or probiotic supplements with the perspective to modulate the gut-brain axis. Full article
(This article belongs to the Special Issue Probiotics and Their Metabolites, 2nd Edition)
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20 pages, 789 KiB  
Review
The Metabolites Produced by Lactic Acid Bacteria and Their Role in the Microbiota–Gut–Brain Axis
by Yulma Lizbeth Aguirre-Garcia, Neftiti Carolina Cerda-Alvarez, Rosa María Santiago-Santiago, Adriana Rocío Chantre-López, Sarahi Del Carmen Rangel-Ortega and Raúl Rodríguez-Herrera
Fermentation 2025, 11(7), 378; https://doi.org/10.3390/fermentation11070378 - 30 Jun 2025
Viewed by 946
Abstract
Lactic acid bacteria (LAB) have historically been used in fermentation processes, playing a key role in the development of foods with health benefits. Understanding the factors that affect LAB functionality is essential for optimizing their application. During fermentation processes, LAB produce different metabolites [...] Read more.
Lactic acid bacteria (LAB) have historically been used in fermentation processes, playing a key role in the development of foods with health benefits. Understanding the factors that affect LAB functionality is essential for optimizing their application. During fermentation processes, LAB produce different metabolites of interest, such as lactic acid, gamma-aminobutyric acid (GABA), and short-chain fatty acids, whose production is influenced by conditions such as temperature and pH. Although LAB exhibit optimal growth ranges, their ability to adapt to moderate variations makes them particularly valuable in various applications. Currently, the impact of these LAB metabolites on human physiology is being actively investigated, especially for modulation of the Microbiota–Gut–Brain axis. Certain compounds derived from LAB have been shown to contribute to neurological, immunological, and metabolic processes, opening new perspectives for the design of functional foods. This article provides a comprehensive overview of the importance of lactic acid bacteria in human health and highlights their potential for the development of innovative strategies to promote well-being through diet. Full article
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31 pages, 519 KiB  
Review
Potential of Pigmented Rice in Bread, Bakery Products, and Snacks: A Narrative Review of Current Technological and Nutritional Developments
by Gemaima C. Evangelista and Regine Schönlechner
Appl. Sci. 2025, 15(12), 6698; https://doi.org/10.3390/app15126698 - 14 Jun 2025
Viewed by 663
Abstract
Rich in bioactive compounds, pigmented rice offers superior antioxidant capacity compared to non-pigmented rice. Processing methods like milling, parboiling, thermal treatments (e.g., extrusion cooking), and biobased approaches (e.g., germination and fermentation) impact the technological and nutritional properties of pigmented rice. All products with [...] Read more.
Rich in bioactive compounds, pigmented rice offers superior antioxidant capacity compared to non-pigmented rice. Processing methods like milling, parboiling, thermal treatments (e.g., extrusion cooking), and biobased approaches (e.g., germination and fermentation) impact the technological and nutritional properties of pigmented rice. All products with added pigmented rice showed improved total phenolic content and antioxidant capacities. Extrusion cooking improved technological properties of dough, bread, and bakery products by modifying the pasting properties of rice. Germination and fermentation enhanced bakery products’ nutritional value by increasing gamma-aminobutyric acid (GABA) levels. Pigmented rice flour can enhance the volume, crumb firmness, and elasticity of gluten-free (GF) bread, especially with ohmic heating. It improved sensory qualities and consumer acceptance of various baked products and extruded snacks. While pigmented rice-based pasta and noodles had compromised cooking qualities, germination improved noodle cooking qualities. Pre-processing techniques like parboiling and micronisation show potential for improving pigmented rice’s technological properties and warrant further study. In conclusion, pigmented rice can enhance the technological and nutritional qualities of bread, bakery products, and snacks. Future researches should focus on agronomic advancement, optimization of pre-processing and processing techniques, exploring varietal differences among pigmented rice cultivars, and promotion of consumer awareness and market potentials. Full article
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20 pages, 1162 KiB  
Article
Involvement of Matrix Metalloproteinases (MMP-2 and MMP-9), Inflammasome NLRP3, and Gamma-Aminobutyric Acid (GABA) Pathway in Cellular Mechanisms of Neuroinflammation in PTSD
by Anna Grzesińska and Ewa Alicja Ogłodek
Int. J. Mol. Sci. 2025, 26(12), 5662; https://doi.org/10.3390/ijms26125662 - 13 Jun 2025
Cited by 1 | Viewed by 532
Abstract
Research into the potential health consequences of trauma indicates that traumatic experiences can disrupt normal biological processes and increase the risk of neuroinflammation and the development of clinical symptoms of post-traumatic stress disorder (PTSD). In this study, we examined the relationship between neuroinflammation [...] Read more.
Research into the potential health consequences of trauma indicates that traumatic experiences can disrupt normal biological processes and increase the risk of neuroinflammation and the development of clinical symptoms of post-traumatic stress disorder (PTSD). In this study, we examined the relationship between neuroinflammation and three specific biomarkers—matrix metalloproteinases MMP-2 and MMP-9, the inflammasome NLRP3, and the inhibitory neurotransmitter GABA—in connection with PTSD symptoms assessed using the PTSD Symptom Scale–Interview for DSM-5 (PSSI-5). The symptoms were categorized into the following domains: re-experiencing, avoidance, alterations in cognition and mood, increased arousal and reactivity, distress and functional impairment, symptom onset and duration, and the total symptom score. Our findings confirmed the pro-inflammatory roles of MMP-2, MMP-9, and the inflammasome NLRP3, as well as the anti-inflammatory, calming effect of GABA. We identified strong correlations between biomarkers, particularly between MMP-2 and MMP-9, MMP-2 and NLRP3, and MMP-2 and GABA, highlighting a closely interconnected inflammatory response. Among the PSSI-5 domains, re-experiencing, increased arousal and reactivity, and distress and functional impairment showed the strongest associations with the total symptom score. Recent research focusing on these cellular mechanisms has provided valuable insights into the role of neuroinflammation in PTSD. These findings enhance our understanding of how inflammation contributes to the disorder’s development and progression. Full article
(This article belongs to the Section Molecular Biology)
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30 pages, 1795 KiB  
Review
Computational Neuroscience’s Influence on Autism Neuro-Transmission Research: Mapping Serotonin, Dopamine, GABA, and Glutamate
by Victoria Bamicha, Pantelis Pergantis, Charalabos Skianis and Athanasios Drigas
Biomedicines 2025, 13(6), 1420; https://doi.org/10.3390/biomedicines13061420 - 10 Jun 2025
Viewed by 3042
Abstract
Autism spectrum disorder is a complex and diverse neurobiological condition. Understanding the mechanisms and causes of the disorder requires an in-depth study and modeling of the immune, mitochondrial, and neurological systems. Computational neuroscience enhances psychiatric science by employing machine learning techniques on neural [...] Read more.
Autism spectrum disorder is a complex and diverse neurobiological condition. Understanding the mechanisms and causes of the disorder requires an in-depth study and modeling of the immune, mitochondrial, and neurological systems. Computational neuroscience enhances psychiatric science by employing machine learning techniques on neural networks, combining data on brain activity with the pathophysiological and biological characteristics of psychiatric–neurobiological disorders. The research explores the integration of neurotransmitter activity into computational models and their potential roles in diagnosing and treating autism using computational methods. This research employs a narrative review that focuses on four neurotransmitter systems directly related to the manifestation of autism, specifically the following neurotransmitters: serotonin, dopamine, glutamate, and gamma-aminobutyric acid (GABA). This study reveals that computational neuroscience advances autism diagnosis and treatment by identifying genetic factors and improving the efficiency of diagnosis. Neurotransmitters play a crucial role in the function of brain cells, enhancing synaptic conduction and signal transmission. However, the interaction of chemical compounds with genetic factors and network alterations influences the pathophysiology of autism. This study integrates the investigation of computational approaches in four neurotransmitter systems associated with ASD. It improves our understanding of the disorder and provides insights that could stimulate further research, thereby contributing to the development of effective treatments. Full article
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26 pages, 724 KiB  
Review
Molecular Basis of Anxiety: A Comprehensive Review of 2014–2024 Clinical and Preclinical Studies
by Ermis Merkouris, Alexandra Brasinika, Meropi Patsiavoura, Chrysanthi Siniosoglou, Dimitrios Tsiptsios, Andreas S. Triantafyllis, Christoph Mueller, Ioulia Mpikou, Myrto T. Samara, Nikolaos Christodoulou and Konstantinos Tsamakis
Int. J. Mol. Sci. 2025, 26(11), 5417; https://doi.org/10.3390/ijms26115417 - 5 Jun 2025
Viewed by 1350
Abstract
Anxiety disorders are among the most common psychiatric conditions that significantly impair one’s quality of life and place a significant burden on healthcare systems. Conventional treatments have certain restraints, such as potential side effects and limited efficacy. Τhe underlying pathophysiological mechanisms of anxiety [...] Read more.
Anxiety disorders are among the most common psychiatric conditions that significantly impair one’s quality of life and place a significant burden on healthcare systems. Conventional treatments have certain restraints, such as potential side effects and limited efficacy. Τhe underlying pathophysiological mechanisms of anxiety are not fully understood. A comprehensive literature search was performed in MEDLINE and Scopus databases for original English-language articles published between January 2014 and December 2024. Study selection, data extraction, and screening were independently carried out by multiple investigators using predefined criteria. Our review aimed to help better comprehend the molecular basis of anxiety, focusing on the hypothalamic–pituitary–adrenal (HPA) axis, serotonergic signaling, and gamma-aminobutyric acid (GABA) neurotransmission. In addition, we addressed the role of epigenetics and pharmacogenomics in personalized treatment. Although novel anxiety treatments are promising, they are predominantly preclinical and highly heterogeneous, which poses a challenge to achieving reliable therapeutic efficacy. Our findings could potentially contribute to the development of new therapeutic interventions. Further research is warranted, especially in human subjects, with an aim to combine genetic and epigenetic profiles to refine treatment approaches and develop innovative therapeutics. Full article
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19 pages, 537 KiB  
Review
Dysregulated Neurotransmitters and CB1 Receptor Dysfunction and Their Roles in Agitation Associated with Alzheimer’s Disease
by Jagadeesh S. Rao, María Alejandra Tangarife, Diego A. Rodríguez-Soacha, María Juanita Arbelaez, María Margarita Venegas, Laura Delgado-Murillo, Saadia Shahnawaz, Claudia Grimaldi, Evelyn Gutiérrez and Ram Mukunda
J. Dement. Alzheimer's Dis. 2025, 2(2), 15; https://doi.org/10.3390/jdad2020015 - 1 Jun 2025
Viewed by 749
Abstract
Alzheimer’s disease (AD) is characterized by the progressive loss of cognitive function and is frequently accompanied by neuropsychiatric symptoms (NPS). Pathologically, AD is defined by two hallmark features: the extracellular accumulation of β-amyloid and the intracellular hyperphosphorylation of the tau protein. In addition [...] Read more.
Alzheimer’s disease (AD) is characterized by the progressive loss of cognitive function and is frequently accompanied by neuropsychiatric symptoms (NPS). Pathologically, AD is defined by two hallmark features: the extracellular accumulation of β-amyloid and the intracellular hyperphosphorylation of the tau protein. In addition to these primary changes, several other abnormalities are associated with the disease, including neuroinflammation, synaptic loss, oxidative stress, neurotransmitter imbalance, and genetic and epigenetic alterations. NPS in AD encompass a range of symptoms, such as anxiety, apathy, agitation, depression, and psychosis. These symptoms are thought to arise partly from the damage caused by the pathological hallmarks of AD, which impair various neurotransmitter systems. Altered levels of several neurotransmitters, including gamma-aminobutyric acid (GABA), serotonin (5-HT), dopamine (DA), and the cholinergic and noradrenergic systems, have been implicated in the development of agitation. Additionally, reduced endocannabinoid system (ECS) functionality, particularly cannabinoid receptor 1 (CB1R), has been linked to neurobehavioral alterations. Preclinical studies suggest that a decrease in CB1R levels is associated with aggressive behavior, and CB1R agonists have demonstrated beneficial effects in alleviating agitation and related symptoms. Given these findings, the current review focuses on the therapeutic potential of targeting neurotransmitter systems and CB1R dysfunction to manage agitation in AD. Full article
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35 pages, 7037 KiB  
Article
In Silico and In Vivo Evaluation of a New Derivative from Memantine and Sinapic Acid (N-Sinapoyl-memantine) as a Candidate for the Management of Alzheimer’s Disease
by Andrey Popatanasov, Lyubka Tancheva, Reni Kalfin and Maya Chochkova
Crystals 2025, 15(6), 491; https://doi.org/10.3390/cryst15060491 - 22 May 2025
Viewed by 465
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease which has a rather complex pathophysiology. During its course, several neurotransmitter neuronal systems get affected such as acetylcholinergic, glutamatergic, gamma-aminobutyric acid (GABA)ergic systems, etc. Such complex physiology requires a sophisticated approach to pharmaceutical [...] Read more.
Alzheimer’s disease (AD) is the most common neurodegenerative disease which has a rather complex pathophysiology. During its course, several neurotransmitter neuronal systems get affected such as acetylcholinergic, glutamatergic, gamma-aminobutyric acid (GABA)ergic systems, etc. Such complex physiology requires a sophisticated approach to pharmaceutical management. Therefore, multi-target drugs seem to be an appealing solution. In the present study, we designed and synthesized a hybrid molecule—N-sinapoylamide of memantine, whose parent molecules memantine (MEM) and sinapic acid have been shown in vivo to impact glutamatergic, acetylcholinergic, and GABA-ergic systems, respectively. In silico comparative testing of these molecules was performed, their patterns of interaction with the target enzymes or molecular complexes were analyzed, and some of the mechanisms of action were proposed. Consequently, in vivo testing was performed on a scopolamine mice model of AD and the results overly confirm part of the in silico findings. Therefore, the hybrid molecule (N-Sinapoyl-memantine) seems to be a potent candidate for further evaluation in the management of AD. Full article
(This article belongs to the Section Biomolecular Crystals)
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33 pages, 2520 KiB  
Review
Relationship Between Obesity and Depression Considering the Inflammatory Theory
by Aleksandra Julia Oracz, Mateusz Zwierz, Maciej Naumowicz, Maria Suprunowicz and Napoleon Waszkiewicz
Int. J. Mol. Sci. 2025, 26(11), 4966; https://doi.org/10.3390/ijms26114966 - 22 May 2025
Cited by 1 | Viewed by 1251
Abstract
Numerous scientific findings indicate that excess adipose tissue, particularly visceral fat, is associated with a chronic inflammatory state manifested by elevated levels of proinflammatory cytokines and an imbalance in the T helper type 1/type 2 (Th1/Th2) response, which carries numerous metabolic consequences. Obesity [...] Read more.
Numerous scientific findings indicate that excess adipose tissue, particularly visceral fat, is associated with a chronic inflammatory state manifested by elevated levels of proinflammatory cytokines and an imbalance in the T helper type 1/type 2 (Th1/Th2) response, which carries numerous metabolic consequences. Obesity induces, among other effects, the activation of the kynurenine pathway and a reduction in serotonin synthesis, alterations in adipokine profiles, modifications of the hypothalamic–pituitary–adrenal (HPA) axis, disturbances in fatty acid ratios, oxidative stress, and dysfunction of the gamma-aminobutyric acid (GABA)ergic system. These neuroimmunological and metabolic disturbances, along with obesity-induced neurotransmission abnormalities that may represent a common underlying model of depression, could provide valuable insights into the pathomechanisms of depression, allowing for prediction of disease progression and individualized therapeutic strategies in overweight patients. Furthermore, the analysis of inflammation-associated biomarkers opens up new therapeutic perspectives, suggesting that interventions aimed at reducing inflammation might lead to potential advances in the treatment of depression. Full article
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18 pages, 4023 KiB  
Article
Lactobacillus brevis GKJOY Supplementation Ameliorates Oxidative Stress and Reproductive Dysfunction in Male Rats with Polystyrene Microplastics-Induced Reproductive Toxicity
by Yi-Yuh Hwang, Sabri Sudirman, Yu-Chen Hsu, Chin-Chu Chen, Fanbin Kong, Deng-Fwu Hwang and Zwe-Ling Kong
Int. J. Mol. Sci. 2025, 26(10), 4533; https://doi.org/10.3390/ijms26104533 - 9 May 2025
Viewed by 703
Abstract
The growing demand for plastic products has led to an increase in human exposure to microplastics (MPs). MPs have been shown to have detrimental effects on reproductive function, while probiotics have demonstrated promise in enhancing fertility. This study aimed to determine the protective [...] Read more.
The growing demand for plastic products has led to an increase in human exposure to microplastics (MPs). MPs have been shown to have detrimental effects on reproductive function, while probiotics have demonstrated promise in enhancing fertility. This study aimed to determine the protective effects of Lactobacillus brevis GKJOY against reproductive damage induced by polystyrene microplastics (PS-MPs) in male rats. In the cell study, LC540 cells were treated with L. brevis GKJOY postbiotic (PGK), gamma-aminobutyric acid (GABA), and PS-MPs to evaluate their effects on cell viability and reactive oxygen species (ROS) production. In the animal experiment, rats were treated with a low dose of L. brevis GKJOY (GK1X, 50 mg/kg), a medium dose (GK2X, 100 mg/kg), or a high dose (GK4X, 200 mg/kg). The results showed that PGK and GABA reduced the levels of ROS and protected against oxidative stress. In contrast, PS-MPs increased ROS levels and had harmful effects on cell viability. In the animal study, testicular injuries caused by PS-MPs led to disruption of the hypothalamic–pituitary–gonadal (HPG) axis and a decrease in reproductive hormone levels. However, treatment with L. brevis GKJOY reduced oxidative stress and pro-inflammatory cytokine levels, restored hormonal imbalances, and led to significant improvements. L. brevis GKJOY effectively mitigated reproductive damage in male rats due to its dual function as a probiotic and neurotransmitter modulator. In conclusion, L. brevis GKJOY, which functions as both a probiotic and a GABA producer, may offer superior protection against male reproductive damage. Full article
(This article belongs to the Section Molecular Pharmacology)
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