Metabolic brain disease最新文献

{"title":"Low carbohydrate and low-calorie diets reduce liver fat and lower brain glutamate and myo-inositol levels in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).","authors":"Andreana P Haley, Jack Knight-Scott, Marie Caillaud, Isabelle Gallagher, Jessica Park, Yanrong Li, Tianyu Wang, Hirofumi Tanaka, Jeffrey D Browning","doi":"10.1007/s11011-025-01624-8","DOIUrl":"10.1007/s11011-025-01624-8","url":null,"abstract":"<p><p>In a longitudinal cohort study with intervention (NCT05216796), we utilized multiorgan imaging to determine if metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with elevated cerebral glutamate and myo-inositol and to determine their sensitivity to dietary intervention. Fifty-five adults with self-reported MASLD or high MASLD risk (3 + metabolic risk factors) received liver and brain magnetic resonance spectroscopy scans pre and post two-week low carbohydrate (≤30 g/d) or low-calorie (women ~ 1200 kcal/d; men ~ 1500 kcal/d) diet, both known for their ability to reduce liver fat. Forty-four adults completed the study (36 female, average age 54 years). Thirty out of 44 met clinical criterion for MASLD based on neuroimaging (≥ 5% hepatic triglycerides). Intervention was associated with significant decreases in liver fat fraction (mean difference = 3.101, 95% CI 2.104-4.099, p < 0.0001), glutamate (mean difference = 0.753, 95% CI 0.274-1.233, p = 0.0032) and myo-inositol (mean difference = 0.478, 95% CI 0.180-0.775, p = 0.0027) in patients with confirmed MASLD. Thus, MASLD may be a source of glutamate neurotoxicity and neuroinflammation and diet is an effective strategy for supporting brain as well as liver health.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"199"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010894","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":"Hepatic encephalopathy in cirrhosis: therapies and developments.","authors":"Ajay Kumar Mishra, Radha Krishan Dhiman","doi":"10.1007/s11011-025-01598-7","DOIUrl":"10.1007/s11011-025-01598-7","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a frequent decompensation in patients with cirrhosis, which significantly affects morbidity and mortality. Ammonia is a major neurotoxin implicated in the pathogenesis, progression, and severity of HE, and various organs including the gut, muscle, kidney, and brain are involved in its metabolism. Therefore, therapeutic management involves reducing ammonia production and increasing its elimination from the blood and the brain. Prevention of HE in patients at high risk of first and recurrent episodes is important for prolonging survival. Various anti-ammonia therapies with synergistic and complementary actions have been attempted for overt HE and for prophylaxis of the first and recurrent episodes of HE. In the current review, we summarize the currently used and under-development pharmacotherapies/procedure(s) for HE in cirrhosis and their mechanism of action. Primary and secondary prophylaxis with monotherapies and combination therapies are also discussed.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"198"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023200","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":"Impact of chronic hyperglycemia and high-fat diet on Alzheimer's disease-related pathology in CX3CR1 knockout mice.","authors":"Andrew Adonay Ortiz, Andrew Scott Murtishaw, Monica Beckholt, Arnold Maloles Salazar, Amanda Marie Leisgang Osse, Jefferson William Kinney","doi":"10.1007/s11011-025-01618-6","DOIUrl":"10.1007/s11011-025-01618-6","url":null,"abstract":"<p><p>Diabetes mellitus (DM), obesity, and metabolic syndrome are related disorders with wide-ranging and devastating effects that are comorbid with many other diseases. Clinical and epidemiological studies have found that type II diabetes mellitus (T2DM), including chronic hyperglycemia and hyperinsulinemia, significantly increases the risk of Alzheimer's disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative disease. To investigate cognitive function and AD-related disease pathology, we utilized two different models of key features of diabetes, one model characterized by hyperglycemia resulting from a diabetogenic compound that selectively targets insulin-producing pancreatic β-cells, and the other model based on diet-induced obesity. Additionally, these diabetic models were combined with fractalkine receptor knockout mice (CX3CR1^-/-), a genetic mouse model of inflammation, to explore the additive effects of multiple AD risk factors. The CX3CR1 receptor has been implicated in modulating neuroinflammation associated with AD, and its dysregulation can exacerbate metabolic disturbances and neurodegenerative markers. We found that diabetic-status, regardless of whether it was drug- or diet-induced, resulted in profound impairments in learning and memory and AD-related alterations within the hippocampus.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"197"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971650","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":"Metabolic dysregulation in amyotrophic lateral sclerosis: insights from ¹H NMR-based metabolomics in a tertiary care center in India.","authors":"Priyanka Gautam, Rahul Yadav, Ranjeet Kumar Vishwakarma, Abhishek Pathak, Chandan Singh","doi":"10.1007/s11011-025-01616-8","DOIUrl":"10.1007/s11011-025-01616-8","url":null,"abstract":"<p><p>Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss, leading to severe physical impairment and mortality. Despite available treatments like Riluzole and Edaravone, their limited efficacy highlights the need for improved understanding of ALS pathology. This study has explored metabolic alterations in North Indian ALS patients using ¹H Nuclear Magnetic Resonance (NMR)-based metabolomics. A case-control study, involving 45 ALS patients and 30 healthy controls (HCs) was performed. Serum samples were analyzed using 600-MHz NMR spectrometer, revealing significant metabolic differences between ALS and HC groups. Multivariate analyses identified nine dysregulated metabolites-pyruvate, glutamine, histidine, isoleucine, leucine, imidazole, arginine, creatinine, and choline-with ROC analysis showing isoleucine as a promising biomarker (AUC 83%). Pathway enrichment analysis highlighted disruptions in key metabolic pathways, including the Glucose-Alanine Cycle, Urea Cycle, Ammonia Recycling, and the Warburg Effect, suggesting potential links to neuroinflammatory and mitochondrial dysfunction in ALS pathogenesis. This pilot study provides insight into ALS-specific metabolic alterations in Indian cohort and demonstrates the potential of these metabolites as diagnostic biomarkers. Our findings identify potential biomarkers that require validation in larger, multi-centric cohorts to support diagnosis, prognosis, and improved management of ALS.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"196"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971651","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":"Hydroxymethyltransferase 2 promotes the development of glioblastoma by mediating WTAP regulation of PTEN N6-methyladenosine modification.","authors":"Meng Wang, Guangwei Sun, Yongzhong Fan, Guozhong Sima, Xifeng Sun, Tao Qiu, Xiangdong Li","doi":"10.1007/s11011-025-01621-x","DOIUrl":"10.1007/s11011-025-01621-x","url":null,"abstract":"<p><p>Characterized by rapid proliferation and therapeutic resistance, glioblastoma (GBM) represents the deadliest primary CNS neoplasm, demonstrating a low survival rate and high mortality rate in patients. This is mainly related to the development of GBM more specifically due to the abnormal metabolism within cells. SHMT2 (serine hydroxymethyltransferase 2) acts as a pivotal metabolic regulator in neoplastic cells, driving one-carbon unit transfer essential for nucleotide biosynthesis. Here, we explored the mechanism of SHMT2 mediated GBM occurrence. In this study, SHMT2 expression was assessed in GBM cells and tissues. In vitro experiments were performed to investigate the functional role of SHMT2. The detailed mechanisms of SHMT2-mediated cell metabolism were addressed. Xenograft model analysis explored the influence of SHMT2 on GBM development. The expression level of SHMT2 in GBM clinical tissues and cell lines is higher than that in normal tissues. The downregulation of SHMT2 inhibits the proliferation ability and metabolic process of GBM cell lines. Mechanism dissection revealed that SHMT2 enhanced phosphatase and tensin homolog (PTEN) N6-methyladenosine (m6A) modification through the endogenous methyl donor SAM mediated by SHMT2 via serine/glycine one carbon metabolic networks. In addition, Xenograft model analysis showed that knockdown of SHMT2 inhibited the development of GBM tumors. SHMT2 promotes the tumorigenesis of glioblastoma by regulating the m6A modification of PTEN.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"195"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990762","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 second act for spironolactone: cognitive benefits in renal dysfunction - a critical review.","authors":"Akhil Sharma, Ashi Mannan, Shareen Singh, Thakur Gurjeet Singh","doi":"10.1007/s11011-025-01623-9","DOIUrl":"10.1007/s11011-025-01623-9","url":null,"abstract":"<p><p>Renal dysfunction or Chronic kidney disease (CKD) are increasingly associated with cognitive deficit and memory impairment, suggesting a crucial kidney-brain axis. This review examines spironolactone's emerging role as a neuroprotective agent in the context of renal dysfunction-induced cognitive impairment. As a selective mineralocorticoid receptor (MR) antagonist, spironolactone demonstrates multifaceted protective mechanisms beyond its well established renoprotective effects. Evidences also suggests that spironolactone attenuates neuroinflammation, mitigates oxidative stress in brain, preserve blood-brain barrier (BBB) integrity and regulates hormonal imbalances associated with renal dysfunction. This review focuses on the reported beneficial effects of spironolactone in various neurodegenerative diseases (NDDs). These mechanisms collectively protect against the neurodegeneration in memory impairment induced by renal dysfunction. The dual action of spironolactone on both renal and cerebral tissues presents a novel therapeutic advantage in addressing this complex pathophysiology. This study elucidates multiple beneficial mechanisms by which spironolactone addresses cognitive impairment associated with renal dysfunction. Spironolactone enhances BBB protection and restores BBB integrity which is often compromised with renal dysfunction. It promotes neuroplasticity (allowing for improved neural adaptation and cognitive function), additionally mediates cerebral blood flow (CBF) ensuring adequate oxygen and nutrient delivery to brain. Spironolactone's anti-inflammatory effects by inhibiting the nuclear factor-kappa B (NF-κB) pathway and modulation of neuregulin1 (NRG1)/v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ERBB4) signaling effectively reduce neuroinflammation that contributes to memory impairment. It also mitigates oxidative stress by targeting NADPH-oxidase (NOX), a major source of reactive oxygen species (ROS) in the central nervous system (CNS). Spironolactone also maintains hormonal balance, particularly regarding aldosterone levels, which become dysregulated in renal dysfunction and negatively impact brain function. These insights provide new possibilities for developing targeted therapies against renal dysfunction-induced memory impairment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"194"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033507","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":"Genotypic and phenotypic characteristics of Turkish patients with phenylalanine metabolism disorders.","authors":"Fatma-Nur Kuzucu, Mustafa Kilic, Abdullah Sezer, Selen Has-Ozhan, Harun Yildiz, Tuba Celen-Yoldas, Fatma-Nese Onat, Melike Uyanik","doi":"10.1007/s11011-025-01582-1","DOIUrl":"10.1007/s11011-025-01582-1","url":null,"abstract":"<p><p>Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe intellectual disability, epilepsy, and behavioural problems. We aimed to investigate demographic, clinical, biochemical, and molecular genetic data in patients with phenylalanine metabolism disorder. This study included 99 predominantly Turkish patients diagnosed with phenylalanine metabolism disorder, primarily referred through newborn screening programs. These patients were evaluated at a single center over a 9-year period, from 2013 to 2021. Demographic, clinical, molecular and laboratory data were collected retrospectively. Among the 99 patients, 93 (93.9%) had hyperphenylalaninemia-phenylketonuria, 2 (2.0%) had tetrahydrobiopterin metabolism disorders [one due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency and the other due to dihydropteridine reductase (DHPR) deficiency], 3 (3.0%) had maternal PKU syndrome (one of whom also had mild phenylketonuria), and 1 (1.0%) had transient hyperphenylalaninemia. The majority of patients belonged to the mild hyperphenylalaninemia-not requiring treatment group. A total of 33 different alleles and 40 genotypes (59.6% compound heterozygous) were identified in the PAH gene, with missense variants accounting for the largest proportion (72.7%). The most frequent PAH gene variants were c.898G > T p.(Ala300Ser) (14.9%), c.1066-11G > A (8.5%), and c.1208C > T p.(Ala403Val) (8.5%), while the most common genotypes were c.898G > T p.(Ala300Ser)/c.898G > T p.(Ala300Ser) (6.4%) and c.898G > T p.(Ala300Ser) /c.1066-11G > A (6.4%), respectively. Among patients with mild hyperphenylalaninemia-not requiring treatment, the predominant genotypes were c.898G > T p.(Ala300Ser)/c.898G > T p.(Ala300Ser) (11.1%), c.898G > T p.(Ala300Ser)/c.1066-11G > A (11.1%), and c.1208C > T p.(Ala403Val)/c.1208C > T p.(Ala403Val) (7.4%), whereas c.842C > T p.(Pro281Leu)/c.842C > T p.(Pro281Leu) (33.3%) was frequently observed in classic PKU patients. The national newborn screening program has significantly improved the prognosis and quality of life for patients through early diagnosis and timely treatment. While the prevalence of hyperphenylalaninemia-phenylketonuria remains high in Turkey, the higher frequency of the hyperphenylalaninemia-not requiring treatment group, compared to European and Asian countries, is considered a favorable outcome. Additionally, the PAH genotype is identified as the primary determinant of the PKU phenotype.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"193"},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990759","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":"Urea cycle defects in adulthood: clinical presentation, diagnosis and treatment in genetically encoded hepatic metabolic disorders with a potential for encephalopathy.","authors":"Anibh Martin Das","doi":"10.1007/s11011-025-01619-5","DOIUrl":"10.1007/s11011-025-01619-5","url":null,"abstract":"<p><p>Hyperammonaemia is an important cause for encephalopathy. Ammonia is the waste product of amino acid degradation and cannot be excreted via urine. Ammonia is metabolized to water-soluble urea via the urea cycle. Hyperammonaemia not only occurs during acute liver failure, but also in rare genetically determined defects of enzymes or transporters involved in the urea cycle resulting in elevated ammonia concentrations. Enzyme defects include deficiency of carbamylphosphate synthase, N-acetylglutamate synthase, ornithine transcarbamylase, argininosuccinate lyase and arginase, transporter defects are citrin deficiency and HHH-syndrome. These urea cycle defects (UCD) mostly manifest for the first time during the neonatal period, infancy or childhood, however first clinical manifestations including encephalopathy may be observed in adulthood in milder forms. Therefore, physicians treating adults should be aware of clinical symptoms in UCD to make a timely diagnosis and initiate treatment. In adulthood, clinical symptoms are often uncharacteristic including headache, avoidance of high-protein food, psychiatric symptoms triggered by heavy exercise or delivery of a child, autism, attention deficit, lethargy, developmental delay and epilepsy. Elevated ammonia concentrations in blood are the biochemical hallmark. Some UCDs can be diagnosed at metabolite level, others only at genetic level. Treatment consists of eucaloric, low-protein diet supplemented with essential amino acids and vitamins/trace elements, and intake of arginine or citrulline. Pharmacological scavengers of nitrogen are benzoate and butyrate. If conservative therapy fails, hemodialysis should be considered. Prompt treatment during acute crises is essential for optimal outcome. Liver transplantation is considered in metabolically unstable patients. For arginase deficiency, enzyme replacement therapy is available.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"192"},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022776","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":"The impact of modafinil on memory and brain oxidative stress: contrasting effects of acute and chronic administration in healthy rats.","authors":"Jorge M Aguiar-Geraldo, Bruno Spalenza da Silva, Taise Possamai-Della, Maria Luísa Machado-Laureano, Aline Vitoreti-Vargas, João Quevedo, Samira S Valvassori","doi":"10.1007/s11011-025-01600-2","DOIUrl":"10.1007/s11011-025-01600-2","url":null,"abstract":"<p><p>The present study assessed the impact of modafinil (MD) on memory function and oxidative damage in the brains of naive rats. Wistar rats were administered either a single dose or repeated doses (over 30 days) of water or MD (75, 150, or 300 mg/kg) via gavage. The novel object recognition (NOR), open-field habituation (OFH), and inhibitory avoidance task (IA) tested the animals' memory. Furthermore, the oxidative and nitrosative stress markers (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], 3-nitrotyrosine [3-nitro], superoxide dismutase [SOD], and catalase [CAT]) were assessed in the frontal cortex, hippocampus and striatum of the rats. The acute administration of MD did not affect any memory measures or oxidative stress parameters evaluated in this study. In contrast, chronic MD administration at a dose of 300 mg/kg decreased memory related to habituation and recognition. In addition, chronic administration of this drug increased oxidative lipid damage, evaluated through 8-ISO and 4-HNE. These findings suggest a potential link between chronic MD use, memory impairment, and oxidative stress in the brains of rats, emphasizing the importance of further research in this area.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"191"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019670","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 network pharmacology-based approach to decipher the pharmacological mechanisms of Salvia officinalis in neurodegenerative disorders.","authors":"Sheikh Sana Nazir, Divya Goel, Divya Vohora","doi":"10.1007/s11011-025-01599-6","DOIUrl":"10.1007/s11011-025-01599-6","url":null,"abstract":"<p><p>The present study aimed to assess the pharmacological mechanism of Salvia officinalis in Neurodegenerative disorders using a network pharmacology approach followed by molecular docking analysis. Phytoconstituents of S.officinalis were obtained from various databases, followed by the screening of active ingredients using the Swiss ADME web tool. Potential targets of active ingredients were identified using PubChem & SwissTargetPrediction. Genes related to Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) were gathered using online databases. Besides, the correlation between active ingredient targets and disease-associated genes was linked. Networks were constructed, visualized, and analyzed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were performed using DAVID database. Decisively, Autodock was used for molecular docking. The results of network analysis identified 9 key active ingredients based on topological analysis of the active ingredient-candidate targets network. Also, the analysis revealed a shared target of 9 key active ingredients of S. officinalis that interacted with 133 AD-related targets whereas only 6 active ingredients interacted with 85 and 58 targets of PD and HD respectively. The core genes from the network were AKT1, BACE1, CASP3, MAPK1, TNF, and IL6. Furthermore, GO and KEGG enrichment analysis showed that FOXO, TNF, MAPK, PI3K-Akt, Rap 1, and neurotrophin signalling pathways as enriched, which were further evaluated by molecular docking suggesting the protective role of S. officinalis in neurodegenerative diseases. Our research reveals the therapeutic benefits of S. officinalis, which might play a crucial role in modulating neurodegenerative diseases.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"190"},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003012","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}