Metabolic brain disease最新文献

{"title":"NREP is involved in xenon's protection against ischemic stroke injury through modulating microglial M1 polarization and neuroinflammation.","authors":"Shuangqiang Yi, Gang Wu, Qianqian Sun, Yunjie Qi, Jinliang Zhou","doi":"10.1007/s11011-026-01931-8","DOIUrl":"10.1007/s11011-026-01931-8","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) is associated with high mortality and disability rates, and secondary neuroinflammation is a key driver of exacerbated neuronal damage. Xenon (Xe) exhibits neuroprotective effects, yet the specific mechanism by which it regulates microglia remains unclear.</p><p><strong>Methods: </strong>Public transcriptome datasets of human stroke cortex (GSE56267) and Xe-treated microglia (GSE273575) were analyzed, and key genes were screened using machine learning. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established with human microglial cells (HMC3). NREP expression, microglial polarization, and inflammatory responses were assessed via Western blot, flow cytometry, and ELISA. HMC3 cells were co-cultured with human cortical neurons using Transwell inserts, and neuronal damage was evaluated by CCK-8 assay, kit-based detection, and flow cytometry. Finally, a middle cerebral artery occlusion (MCAO) model was established in rats to investigate the potential involvement of NREP in the neuroprotective effects of Xe in vivo.</p><p><strong>Results: </strong>NREP was identified as a key regulatory gene that was downregulated after stroke and upregulated following Xe treatment. In the OGD/R model, Xe upregulated NREP expression in HMC3 cells, inhibited M1 polarization and proinflammatory cytokine release, and this effect could be partially reversed by NREP silencing. Xe-treated HMC3 cells mitigated apoptosis and oxidative stress in co-cultured neurons, which appeared to be, at least in part, dependent on NREP. In MCAO rats, Xe upregulated NREP in the brain and reduced infarct volume and neuroinflammation. Critically, in vivo knockdown of NREP significantly reversed these neuroprotective and anti-inflammatory effects of Xe.</p><p><strong>Conclusion: </strong>Xe treatment upregulated NREP expression, inhibited M1 polarization of microglia and neuroinflammation, and alleviated cerebral ischemia-reperfusion injury in experimental models. These findings suggest that NREP contributes to xenon-mediated neuroprotection and may serve as a potential therapeutic target, providing preliminary experimental evidence for subsequent translational research of IS.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-target approach using Moringa oleifera leaf extract in ameliorating PTZ-induced epilepsy-like neurobehavior in male rats: in vivo and in silico study.","authors":"Amina E Essawy, Esraa S Elfiky, Sherine Abdel Salam, Nema A Mohamed, Howida A Fetouh, Ahmed S Al-Shami, Wessam M Abdel-Wahab","doi":"10.1007/s11011-026-01928-3","DOIUrl":"10.1007/s11011-026-01928-3","url":null,"abstract":"<p><p>Although a variety of antiepileptic medications are available, their administration often leads to undesirable side effects. In the present study, we investigated the effect of Moringa oleifera leaf extract (MOLE) against neurodegenerative pathophysiology relevant to PTZ-induced epilepsy-like neurobehavior in the hippocampus of rats. Forty male rats were allocated into four groups: control group, MOLE group, PTZ group, and PTZ plus MOLE group. MOLE (300 mg/kg) was administered orally for 35 days, while PTZ (40 mg/kg) was injected intraperitoneally in nine doses on alternate days, commencing on the 18th day. Phytochemical analysis using GC-MS and molecular docking was performed. Animals were behaviorally assessed using open field and elevated plus maze tests. The hippocampal tissue was evaluated for malondialdehyde, nitric oxide, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, tumor necrosis factor-α, interleukin-1β and 6, acetylcholine, acetylcholinesterase, gamma-aminobutyric acid, glutamate, and monoamine oxidase. NF-kB expression, histopathological alterations, caspase-3, and GFAP immunoreactivity were investigated. The GC-MS analysis revealed the presence of various phytochemicals. MOLE attenuated PTZ-induced behavioral changes and improved the oxidant/antioxidant status of the hippocampus. MOLE also reduced the pro-inflammatory cytokines, modulated the neurochemicals, and regulated the expression of NF-κB. Furthermore, MOLE improved the histopathological and the immunohistochemical deteriorations in the hippocampus. Molecular docking analysis showed robust binding affinities for the major phytochemicals to proteins involved in neuroinflammation, oxidative stress, and regulation of neurotransmission. These findings highlight the efficacy of MOLE as a potential multi-target approach against PTZ-induced epilepsy-like neurobehavior, attributed to its diverse bioactive phytochemicals with antioxidative, anti-inflammatory, neuromodulator, and NF-κB regulatory properties.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing apremilast for alzheimer's disease: multitarget modulation of cAMP‑PI3K/Akt-GSK‑3β and NF‑κB signaling.","authors":"Nitish Choudhary, Shakshi Rana, Kanika Vashisht, Varun Sharma, Vandana Bhatia, Mahendra Singh Ashawat, Shiv Kumar Kushawaha","doi":"10.1007/s11011-026-01906-9","DOIUrl":"10.1007/s11011-026-01906-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the leading cause of dementia worldwide, represents a growing global health challenge driven by population aging, the absence of effective disease-modifying therapies, and its inherently multifactorial pathogenesis. This pathogenesis is characterized by amyloid-β (Aβ) aggregation, tau hyperphosphorylation, persistent neuroinflammation, oxidative stress, and synaptic dysfunction. Conventional single-target interventions have consistently failed against this complex interplay of molecular events, thereby highlighting the need for multitarget, systems pharmacology approaches capable of simultaneously modulating convergent pathways. Apremilast (APR), an FDA-approved, orally bioavailable phosphodiesterase-4 (PDE4) inhibitor, has recently emerged as a favorable drug repurposing candidate capable of elevating intracellular cAMP and triggering a cascade of neuroprotective mechanisms. Preclinical investigations from Aβ-challenged neuronal cultures to high-fat diet/streptozotocin-induced rodent models of AD demonstrate that APR attenuates Aβ-induced cytotoxicity, improves cognitive performance, and preserves neuronal and synaptic integrity. Mechanistically, APR mitigates NF-κB-mediated neuroinflammation through IκBα stabilization, thereby reducing the release of proinflammatory cytokines such as TNF-α and IL-6; activates the Nrf2/HO-1 antioxidant defense pathway, and, via cAMP-dependent PI3K/Akt signaling, inhibits GSK-3β to prevent tau hyperphosphorylation, synaptic loss, and neuronal degeneration. This review synthesizes current mechanistic evidence supporting apremilast as a potential multitarget repurposing candidate in AD, thereby addressing key knowledge gaps in the current literature. All supporting evidence was compiled from peer-reviewed sources indexed in PubMed, Web of Science, and Scopus. Guided by network pharmacology and systems biology frameworks, APR's polypharmacological profile positions it as a compelling multitarget candidate for advanced in vivo validation, human iPSC-derived neuronal studies, and AI-driven therapeutic discovery pipelines.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB/COX-2/IL-6 inflammatory pathway.","authors":"Ahmed I Yousef, Sanaa M Abd El-Twab, Sally M Khadrawy, Adel Abdel-Moneim, Rehab G Khalil","doi":"10.1007/s11011-026-01925-6","DOIUrl":"10.1007/s11011-026-01925-6","url":null,"abstract":"<p><p>Impaired insulin function and persistent hyperglycemia damage the brain of diabetics and raise the risk of Alzheimer's disease (AD). Although polydatin (PLD) possesses promising biological effects, no major study has yet explored its anti-neurodegenerative efficacy in the hippocampus. This study therefore aims to investigate the probable protective effects of PLD against hippocampal neurodegeneration in diabetic rats, as well as explore its in-silico inhibitory activity against two key enzymes implicated in the progression of AD. Experimental diabetes was induced in male albino rats then PLD was administered orally to the diabetic rats (50 mg/kg b.wt.) daily for four weeks. In silico molecular docking was used to predict the interactions of PLD against BACE1 and AChE. PLD treatment significantly improved diabetic parameters, lowering blood glucose and raising serum insulin. Excitingly, PLD markedly alleviated oxidative stress by reducing lipid peroxidation and nitric oxide levels while enhancing antioxidant defenses (elevated GPx activity and GSH content) in the hippocampus of diabetic rats. PLD also suppressed neuroinflammation by down-regulating NF-κB, COX-2, and IL-6 mRNA expression. Furthermore, PLD significantly elevated the protein level of IDE while lowered Aβ_1-42 level. In silico, PLD revealed potent binding affinity for BACE1 (-8.6 Kcal/mol) and AChE (-10.5 Kcal/mol), interacting with key residues, indicating its inhibition potential. Overall, PLD effectively reduced neurodegeneration in the hippocampus of diabetic rats via inhibiting oxidative stress, inflammation, and Aβ_1-42 accumulation. PLD may act as a promising multi-target anti-neurodegenerative candidate, capable of simultaneously modulating multiple pathways and more experimental validation are needed in the future.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychological and metabolic interconnectivity in obesity, anorexia and bulimia nervosa - an integrative literature review.","authors":"Malini Turner, Mansi Dass Singh, Ian Evans","doi":"10.1007/s11011-026-01892-y","DOIUrl":"10.1007/s11011-026-01892-y","url":null,"abstract":"<p><p>A dysfunctional bi-directional signalling of plural neural networks expresses distinct metabolic disruption with mental health consequences in obesity, anorexia nervosa and bulimia nervosa. Maladaptive brain-gut connectivities lead to multifactorial contributing factors raising the interest of researchers in an effort to address their neurobiological, psychological and metabolic factors to improved mental health outcomes. The first aim of this review was to collate clinical evidence on brainstem-hypothalamus pathways in obesity, anorexia nervosa and bulimia nervosa. Further, it sought to describe the chief brain-based interactions within both the brain-gut and brain-gut-adipose axis in these conditions. Another aim was to explore the interactions of prominent peptides within the brain-gut and brain-gut-adipose axes. The final aim was to integrate the knowledge of maladaptive neural, peptide and hormonal signalling interactions with the mental faculty. According to integrative review guidelines, the multileveled information was grouped into three superordinate themes: the brain neurofeedback, the stomach neurofeedback and the sympathoadrenal neurofeedback, with seven subordinate themes: brain stem, lateral nucleus of the hypothalamus, arcuate nucleus of the hypothalamus, mechanism of appetite regulation, short-term satiety and long-term satiety signalling as well as the mechanisms of glucoprivation and lipoprivation, presented in Table 1. Their interconnectivites are synthesised in seven Figures, presented at each subtheme section. This paper augmented our understanding of brain maladaptive interactions with gut peptides and hormones among people with obesity and eating disorders and may serve a roadmap to neurobiological and metabolic influences on physical and mental health. Limitations identify qualitative areas of research towards evidence-informed psychiatric and health counselling support.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced cortical gyrification in type 1 diabetes is associated with white matter integrity loss and cognitive decline.","authors":"Jonadab Dos Santos Silva, Richard G IJzerman, Martin Klein, Frederik Barkhof, Annette C Moll, Frank J Snoek, Eelco van Duinkerken","doi":"10.1007/s11011-026-01926-5","DOIUrl":"10.1007/s11011-026-01926-5","url":null,"abstract":"<p><p>Type 1 diabetes-related cognitive declines suggest cortical involvement, despite cortical volume and thickness failing to account for these changes. The local gyrification index (LGI), which quantifies the complexity of cortical folding, could therefore provide additional information about cerebral integrity. This study aimed to determine differences in LGI in type 1 diabetes (T1D) in relation to the white matter integrity of connecting fibers and cognitive functioning. Fifty-one T1D participants with microangiopathy, 53 without, and 49 healthy controls underwent MR-imaging and neuropsychological assessment. LGI was calculated using FreeSurfer6. Probabilistic tractography was performed with MRtrix3. Group analyses were adjusted for age, sex, systolic blood pressure; and for multiple comparisons using Family Wise Error (FWE). Mediation analysis was performed with Python. LGI was broadly reduced across T1D participants, primarily driven by those with microangiopathy (all P_FWE < 0.05), especially in cortical areas connected by the arcuate fasciculus and forceps major. Lower LGI was associated with poorer arcuate fasciculus and forceps major integrity - tracts selected because their fibers connect the cortical regions exhibiting decreased gyrification in type 1 diabetes - and cognition (all P < 0.05). Mediation analyses revealed that cortical gyrification partly mediates the relationship between lower white matter integrity and reduced cognitive performance. LGI reductions had a posterior predominance in the brain in adults with T1D and microangiopathy, and associated with cognitive decrements and poorer white matter integrity. Mediation analyses further suggested a critical role of reduced cortical gyrification in linking lower white matter integrity to poorer cognitive performance.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific gut microbiota and metabolite signatures in Parkinson's disease: implications for personalized therapeutics.","authors":"Sushree Abhidhatri Sharma, Manorama Patri","doi":"10.1007/s11011-026-01924-7","DOIUrl":"10.1007/s11011-026-01924-7","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by dopaminergic neuron loss and α-synuclein aggregation in the substantia nigra pars compacta (SNpc). It is a multifactorial disorder with motor and non-motor manifestations and growing evidence suggests that gastrointestinal dysfunction may precede motor onset. Sex differences influence PD risk, onset and clinical features, with men exhibiting higher prevalence and earlier onset, driven by hormonal, genetic, and metabolic factors. The gut microbiota communicates bidirectionally with the central nervous system (CNS) via the gut-brain axis, modulating neural, immune and metabolic processes. Gut dysbiosis and altered microbial metabolites contribute to PD pathogenesis, with distinct sex-specific differences in the microbial composition and functional dynamics of gut microbiota. Despite growing evidence linking the gut-brain axis to PD, sex-specific regulation of microbiota-metabolite interactions remains poorly understood, representing a critical knowledge gap. Further most studies are male-biased, neglecting sex-specific variations in microbial profiles, hormone dynamics, metabolic responses and treatment outcomes. This review addresses current evidence on sex-specific interactions between gut microbiota, metabolites, microbial metabolites and PD mechanisms, highlighting their role in oxidative stress, neuroinflammation, glial dysfunction and genetic predisposition. It further emphasizes the need for sex-tailored, precision therapeutic strategies integrating hormonal, genetic and microbial determinants to improve clinical PD outcomes.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transthyretin at the crossroads of neurodegeneration: a silent guardian in Parkinson's disease.","authors":"Priti Dipa, Khadga Raj Aran","doi":"10.1007/s11011-026-01907-8","DOIUrl":"10.1007/s11011-026-01907-8","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by disruption of brain homeostasis and degeneration of dopaminergic neurons in the substantia nigra. PD is characterised by motor symptoms, like tremor, rigidity, bradykinesia, and postural instability, as well as non-motor symptoms like cognitive impairment, mood disorders, sleep disturbances, and autonomic abnormalities that significantly affect quality of life. The molecular pathogenesis of PD involves Oxidative stress, neuroinflammation, mitochondrial dysfunction, α-synuclein (α-syn) misfolding and aggregation, insufficient autophagy-lysosomal clearance, and synaptic degeneration, leading to progressive neuronal loss. Transthyretin (TTR), a tetrameric transport protein that is primarily produced in the liver and choroid plexus, is well-known for carrying thyroxine and retinol-binding protein. Experimental studies have shown that TTR can protect neurons by binding misfolded proteins, such as α-syn, decreasing toxic aggregation, regulating oxidative stress responses, and affecting selective autophagic degradation. PD-related changes in TTR expression in brain tissue and cerebrospinal fluid provide strong evidence of TTR's significance as a molecular biomarker and a physiological regulator in the pathogenesis of the disease. This review highlights TTR involvement in neuroinflammation, oxidative stress, and α-syn aggregation, and discusses emerging evidence supporting TTR stabilizers as potential biomarkers and therapeutic targets for modulating disease progression in PD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and structural characterisation of alzheimer's disease associated variants in an Eastern Indian cohort.","authors":"Dipanwita Sadhukhan, Adreesh Mukherjee, Izaz Monir Kamal, Shreyosi Maitra, Brahmachari Somnath Vedeshachaitanya, Bidisha Bhattacharyya, Atanu Biswas, Saikat Chakrabarti, Arindam Biswas","doi":"10.1007/s11011-026-01929-2","DOIUrl":"10.1007/s11011-026-01929-2","url":null,"abstract":"<p><p>Alzheimer's disease (AD) shows substantial clinical heterogeneity often caused by genetic variants contributing to both familial and early-onset forms. However, the genetic landscape of AD in the diverse Indian population remains further characterised. To identify probable pathogenic variants associated with AD, representing individuals from Eastern India and to assess their potential structural effects using molecular dynamics (MD) simulations. Whole-exome sequencing was performed in 29 radiologically confirmed AD patients. Variants identified were screened using standard in silico prediction tools and categorised according to their involvement in amyloid precursor protein (APP)-related and non-APP pathways. Molecular dynamics simulations of filtered variants in PSEN1, SORL1, and ABCA7 genes were conducted using GROMACS 2024 to assess conformational stability, flexibility (RMSD, RMSF), compactness (Rg), and solvent accessibility (SASA). Thirty-six variants across 18 genes were identified, including five pathogenic variants and 31 variants of uncertain significance. Frequently affected genes included ABCA7 (8 variants), SORL1 (3 variants), PSEN1 (two novel variants), and APP (London mutation, Val717Ile). Most patients (83.3%) had a positive family history, with a mean age at onset of 54.17 ± 11.74 years, presenting with typical AD, posterior cortical atrophy, or frontal variants. MD simulations revealed increased rigidity, altered electrostatic interactions, and disrupted ATP-binding dynamics in mutant proteins compared with wild type. This study identifies novel and known AD-associated variants in an Indian cohort and demonstrates their potential structural impact. Integrating genetic and structural analyses provides valuable insights into AD pathogenesis in underrepresented populations.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic mutations and synaptic dysfunctions in social interaction disorders: insights from invertebrate models to humans.","authors":"Victor Ebube Anadu, Toheeb O Oyerinde, Tolulope J Gbayisomore, David A Oyeniran, Francis T Adeniran, Olayemi K Ijomone, Omamuyovwi M Ijomone","doi":"10.1007/s11011-026-01921-w","DOIUrl":"10.1007/s11011-026-01921-w","url":null,"abstract":"<p><p>Abnormal social interactions are key features of various neurodevelopmental and neuropsychiatric disorders, including autism, attention-deficit/hyperactivity disorder, and schizophrenia. Social interaction behaviours are highly conserved and have evolved across species. Studying social behaviours is crucial as it determines an organism's survival, development, and reproduction. Research over the years has demonstrated how genetic mutations influence synaptic architecture and function, revealing their contributions to these social abnormalities. Furthermore, specific genes, known as cell adhesion molecules (CAM), play important roles in the formation, maturation, and functioning of the synapses, and mutations in these genes alter normal synaptic formation and functioning, consequently disrupting behavioural outcomes. In biological systems, normal synaptogenesis has functional implications for social behaviours necessary for social bonding and cooperation. This review integrates findings from studies across various model organisms-including the C. elegans, Drosophila melanogaster, Zebrafish, and rodents- to elucidate how alterations in synaptic function disrupt social interaction. We extensively discuss how mutations in CAM genes alter key conserved synaptic pathways, leading to neurochemical alterations that contribute to social deficits common in neurodevelopmental disorders, as well as therapeutic strategies inspired by animal studies, including the use of drugs and gene therapies in the management and treatment of the symptoms observed in social interaction disorders.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}