Metabolic brain disease最新文献

{"title":"Integrating network pharmacology and experimental validation deciphers the improving effect and mechanisms of Shenwu Yizhi capsule on cognitive impairment in vascular dementia rats.","authors":"Yilan Zhen, Xueqing Wang, Jingwen Niu, Daokang Chen, Cunbao He, Guoqi Zhu, Wenming Ban","doi":"10.1007/s11011-025-01690-y","DOIUrl":"https://doi.org/10.1007/s11011-025-01690-y","url":null,"abstract":"<p><p>The therapeutic mechanisms of Shenwu Yizhi Capsule (SWYZC), a widely used treatment for vascular dementia (VD), remain unclear. This study integrated network pharmacology and experimental methods to elucidate the effects and mechanisms of SWYZC on cognitive function in VD rats. A VD model was established via bilateral common carotid artery occlusion (2-VO). Cognitive function was evaluated using the Morris water maze (MWM), and hippocampal neuronal morphology was assessed via hematoxylin-eosin (HE) staining. Active compounds and targets of SWYZC were identified using the TCMSP, PubChem, and Swiss Target Prediction databases, while VD-related targets were retrieved from OMIM, TTD, and GeneCards. Venny 2.1.0 identified overlapping targets between SWYZC and VD. The STRING database analyzed protein-protein interaction (PPI) networks, and the DAVID database conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Apoptosis and dendritic function were evaluated to explore therapeutic mechanisms. Molecular docking was performed using AutoDock Vina. SWYZC significantly ameliorated cognitive deficits and hippocampal neuronal damage. PPI network analysis identified 20 key targets between SWYZC and VD, including TP53, SRC, CASP3, etc. GO and KEGG analyses indicated that apoptosis, inflammation, and synaptic injury targets were central to SWYZC's therapeutic effects on VD. Moreover, experimental validation demonstrated that SWYZC significantly upregulated PSD95 and PGC-1α expression while downregulated Cleaved Caspase-3, Bax, and connexin43 (CX43) levels. Molecular docking indicated that celabenzine exhibited strong binding to Bax and CX43. Collectively, SWYZC improves memory function and mitigates hippocampal neuronal damage in VD rats by inhibiting apoptosis and promoting synapse formation.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"259"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006325","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":"High-dose acetaminophen does not acutely compromise blood-brain barrier permeability in mice.","authors":"Sumaih Zoubi, Dhavalkumar Patel, Yeseul Ahn, Ehsan Nozohouri, Heba Ewida, Ulrich Bickel","doi":"10.1007/s11011-025-01696-6","DOIUrl":"10.1007/s11011-025-01696-6","url":null,"abstract":"<p><p>Acetaminophen is widely recognized for its safety as a pain reliever and fever reducer at recommended doses. However, in addition to the well-known hepatotoxic and nephrotoxic effects at overdoses recent animal studies in rats have raised the possibility that acetaminophen at a high dose of 500 mg/kg may lead to acute impairment of the blood-brain barrier (BBB). Because species differences in hepatic and renal toxicity of acetaminophen are present, we assessed here the effect of moderate and severe overdoses of acetaminophen (300 mg/kg and 600 mg/kg, respectively) after intraperitoneal administration in mice on BBB permeability. Using stable isotope-labeled [¹³C₁₂]sucrose as a small molecule hydrophilic marker the brain uptake clearance K_in was measured. Our results showed no significant differences in BBB permeability between vehicle control and acetaminophen treated groups (K_in of the control group = 0.070 ± 0.025 µL min^-1 g^-1, K_in of the 300 mg/kg group = 0.059 ± 0.017 µL min^-1 g^-1, and K_in of the 600 mg/kg group = 0.066 ± 0.010 µL min^-1 g^-1, all values mean ± SD, n = 6) suggesting that even high doses of acetaminophen do not acutely compromise BBB permeability in mice. We did also not observe significant changes in tight junction proteins in brain. These findings support the notion that acetaminophen effects on the BBB may be species-specific among rodents.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"258"},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961418","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":"Cannabidiol regulates apoptosis and glial cells homeostasis in the prefrontal cortex of offspring from obese rat mothers.","authors":"Yasmin Meireles Bitencourt, Fernanda da Silva Rodrigues, Gabriel de Farias Fraga, Jeferson Jantsch, Fernanda Wickert, Victor da Silva Dias, Sheila Parnoff de Matos, Keli Cristine Reiter, Giuliano Rizzotto, Márcia Giovenardi, Renata Padilha Guedes","doi":"10.1007/s11011-025-01687-7","DOIUrl":"https://doi.org/10.1007/s11011-025-01687-7","url":null,"abstract":"<p><p>Maternal obesity during pregnancy poses significant health risks for both mother and progeny, including long-term impacts on brain function. In previous studies, we demonstrated that cafeteria diet (CAF) consumption during gestation induces neuroinflammation and behavioral deficits in the offspring, which are reversed by cannabidiol (CBD) treatment. However, the effects of CBD on apoptosis-related pathways in this context remain unclear. Here, we investigated whether CBD treatment can modulate pro-apoptotic signaling and glial cells morphology in adult offspring of obese mothers. Wistar rats were fed a CAF for 12 weeks before mating, during pregnancy, and lactation. Offspring received oral CBD (50 mg/kg) for 3 weeks starting at postnatal day 70. In the prefrontal cortex, we assessed apoptosis-related proteins, TNFα gene expression, and astrocytes and microglia morphology. Male and female offspring of CAF-fed dams showed increased levels of BAD, which were mitigated by CBD treatment. JNK was also elevated in female offspring of obese mothers, and CBD reduced this increase. In females, CBD treatment led to a decrease in AKT concentrations. TNFα expression was elevated in the prefrontal cortex of male offspring of obese mothers. Additionally, a reduction in GFAP- and IBA-1-positive cells in the prefrontal cortex was observed in male offspring of obese dams, which was reversed by CBD. These findings suggest that maternal obesity promotes a pro-apoptotic and inflammatory brain environment, and CBD may counteract these effects via modulation of glial activity and apoptotic pathways.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"256"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961423","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":"Zinc oxide nanoparticles exposure disrupts brain redox-inflammatory-epigenetic axis and impairs PI3K/Akt survival pathway in male offspring.","authors":"Norah Saeed Al-Zahrani, Hind Zafrah, Alshehri Hanan Hassan, Eman Mohamad El Nashar, Hanan M A El Henafy","doi":"10.1007/s11011-025-01699-3","DOIUrl":"https://doi.org/10.1007/s11011-025-01699-3","url":null,"abstract":"<p><p>Widespread use of Zinc Oxide Nanoparticles (ZnO NPs) raises concerns about potential health risks, particularly following maternal exposure during critical developmental windows. The impact of exposure on offspring brain development remains unclear. The work aims to investigate the neurodevelopmental consequences of maternal ZnO NP exposure during gestation, lactation, or both periods in male rat offspring. Pregnant rats were administered ZnO NPs (< 100 nm) or vehicle. Offspring developmental parameters and brain tissues were analyzed at postnatal day 60. Assessments included oxidative stress markers (8-OHdG, MDA, NO), antioxidant (GSH, GST, GPX, SOD, CAT), cholinergic function (AChE), epigenetic markers (DNA methylation, BDNF promoter methylation, miR-34a, miR-29b), neurodegeneration-associated proteins (Aβ1-42, Tau), survival/inflammatory signaling pathways (p-Akt, PI3K mRNA, ERK, Bcl-2, COX2, IL-1β, TNF-α, IL-2, TGF-β), apoptosis (Caspase-3), BDNF mRNA, and brain histology. Maternal ZnO NP exposure significantly reduced offspring brain weight, body weight, and survival index, particularly following combined gestational and lactational exposure. Exposed offspring brains exhibited increased oxidative stress, depleted antioxidant defenses, impaired AChE activity, global DNA hypomethylation with targeted BDNF promoter hypermethylation (correlating with reduced BDNF mRNA), increased Aβ1-42 and Tau accumulation, suppressed PI3K/p-Akt and ERK survival signaling, elevated pro-inflammatory markers (IL-1β, TNF-α, IL-2, COX2, TGF-β), increased apoptosis (Caspase-3) alongside decreased Bcl-2, and dysregulated miRNA expression (increased miR-34a, decreased miR-29b). Histology confirmed duration-dependent neuronal damage. Maternal ZnO NP exposure induces persistent offspring neurotoxicity via oxidative stress, neuroinflammation, apoptosis, and epigenetic dysregulation. This highlights developmental brain vulnerability and the importance of assessing maternal nanoparticle exposure.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"257"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961440","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":"Neurotoxic effects of acyclovir: impacts on oxidative stress, inflammation, and neurotransmitter dynamics in male Wistar rats.","authors":"O O Obembe, R A Mustapha, E T George, A A Bayo-Olugbami, O S Tokunbo, R E Akhigbe","doi":"10.1007/s11011-025-01694-8","DOIUrl":"https://doi.org/10.1007/s11011-025-01694-8","url":null,"abstract":"<p><strong>Background: </strong>Acyclovir is a potent antiviral agent with variable side effects on the central nervous system. Although previous studies have shown that acyclovir has neurotoxic effects, there is a dearth of scientific information on the mechanisms through which acyclovir induces neurotoxicity.</p><p><strong>Aim: </strong>Thus, the present study assessed the impact of acyclovir on oxidative stress, inflammatory markers, and neurotransmitter levels in the cerebellum, prefrontal cortex, and basal ganglia and its potential impact on cognition and motor function.</p><p><strong>Materials and methods: </strong>Twenty-eight male Wistar rats (120-150 g) were randomly assigned into four equal groups. The control group received distilled water while acyclovir-treated groups received single daily treatment at doses of 10, 20, and 40 mg/kg bw orally for 28 days.</p><p><strong>Results: </strong>Acyclovir, at 20 and 40 mg/kg but not at 10 mg/kg, induced a decline in memory, spatial learning, and motor coordination when compared with the control. Also, the brain levels of antioxidants (catalase, superoxide dismutase, and glutathione) and anti-inflammatory cytokine IL-10 were significantly reduced while malondialdehyde and pro-inflammatory cytokines (IL-6 and TNF-α) were increased in the cerebellum, prefrontal cortex, and basal ganglia in acyclovir-treated rats, particularly in those treated with 20 and 40 mg/kg. Serotonin levels increased while dopamine levels decreased in the brain tissues of acyclovir-treated rats. However, IL-1β was not significantly affected.</p><p><strong>Conclusion: </strong>Acyclovir impaired motor function, muscle strength, and memory by inducing derangement of the brain's oxidative markers, cytokines, and neurotransmitter levels.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"255"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961452","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":"Intrauterine growth restriction (IUGR) modifies the hypothalamic response to a systemic glucose load in adult male rats, as assessed by proteomic analysis.","authors":"Thais A J Mutran, Amanda P Pedroso, Adriana P de Souza, Valter T Boldarine, Antonio M M Neto, Claudia B Angeli, Lila M Oyama, Giuseppe Palmisiano, Eliane B Ribeiro, Monica M Telles","doi":"10.1007/s11011-025-01675-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01675-x","url":null,"abstract":"<p><p>We have previously demonstrated that 4-month-old IUGR male rats had obesity, hyperglycemia, and increased hypothalamic glucose levels, indicative of disruption of hypothalamic glucose metabolism. To evaluate, by proteomic analysis, the hypothalamic response to a systemic glucose load before the development of IUGR-induced obesity. Wistar rats were fed either ad libitum (Control group, C) or received 50% of C intake throughout pregnancy (Restricted group, R), and fed ad libitum during lactation. The male C and R offspring were fed ad libitum from weaning to 3-months-old. They were injected intraperitoneally with either saline (CS and RS) or 2 g/kg glucose (CG and RG) (n = 4 each), euthanized after 45 min., and had their hypothalami harvested. Pathway search was conducted with significantly modulated proteins (Student's t-test, p < 0.05). When comparing CS and RS, the tricarboxylic acids cycle and the respiratory chain pathways had multiple down-regulated proteins. Comparing CG and RG, while these pathways were also affected, only pyruvate dehydrogenase complex (PDH) (Fold change (FC) 0.63) was down-regulated while citrate synthase (FC 1.43) and respiratory chain complex I (FC 1.63) were up-regulated. This could represent a compensatory response aimed at overcoming the down-regulation of the respiratory chain induced by IUGR. These seemingly beneficial responses may, however, induce increased reactive oxidative species, insulin resistance and obesity. The results suggest that, even before the establishment of obesity and hyperglycemia, IUGR may have impacted metabolic pathways and the hypothalamic response to a systemic glucose load, that in the long term, could have a negative impact on energy homeostasis.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"250"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961447","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":"Circ_0049472 downregulation relieves Amyloid-β-induced neuronal injury by modulating PDE4A expression via targeting miR-22-3p in Alzheimer's disease.","authors":"Jiao Chen, Sai Xiao, Xiaojie Cui, Xiao Gao, Danyang Wang, Xiaoming Li, Wenbo Qi, Bailing Wang","doi":"10.1007/s11011-025-01652-4","DOIUrl":"https://doi.org/10.1007/s11011-025-01652-4","url":null,"abstract":"<p><p>Neuronal injury is a common event in the development of Alzheimer's disease (AD). Previous studies have suggested that circular RNAs (circRNAs) are involved in neuronal injury in the pathological progression of AD. However, the potential role of circ_0049472 in the AD process is still unclear. Amyloid-β (Aβ)-treated SK-N-SH and CHP212 cells were used as the cell model of AD in vitro. The expression of circ_0049472, miR-22-3p, and phosphodiesterase 4A (PDE4A) was measured by quantitative real-time PCR (qPCR). Cell viability, proliferation, and apoptosis were estimated by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (bcl-2), Bcl-2 related X protein (bax), cleaved-caspase 3, PDE4A, and Postsynaptic protein-95 (PSD-95) were determined using western blot. Interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) levels were analyzed using enzyme-linked immunosorbent assay (ELISA). JC-1 assay was utilized to evaluate mitochondrial function. Binding between miR-22-3p and circPLAR1 or PDE4A was predicted and verified using dual-luciferase reporter assay or RNA Immunoprecipitation (RIP) assay. Circ_0049472 and PDE4A were overexpressed in Aβ-treated SK-N-SH and CHP212 cells, and miR-22-3p was reduced. Knockdown of circ_0049472 might abolish Aβ-mediated proliferation inhibition and the promotion of apoptosis and inflammation, mitochondrial dysfunction in SK-N-SH and CHP212 cells. Mechanistically, circ_0049472 is competitively bound to miR-22-3p to elevate its target PDE4A. Circ_0049472 knockdown alleviated Aβ-induced SK-N-SH and CHP212 cell dysfunctions via targeting the miR-22-3p/PDE4A axis, suggesting that circ_0049472 knockdown might protect from neuronal injury in AD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"252"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961467","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":"Neuroprotective effects of Yangming-Kaixin-Yizhi formula in Alzheimer's disease: dual regulation of PI3K/Akt and p38 MAPK signaling via network pharmacology and experimental approaches.","authors":"Jing Lei, Jiaming Li, Wei Wu, Rui Xiong, Yao Liu, Yong Tang","doi":"10.1007/s11011-025-01688-6","DOIUrl":"https://doi.org/10.1007/s11011-025-01688-6","url":null,"abstract":"<p><p>As a neurodegenerative disease characterized by progressive cognitive decline, the pathogenesis of Alzheimer's disease (AD) is still poorly understood, and there is no effective cure currently available. Traditional Chinese medicine (TCM) prescription Yangming-Kaixin-Yizhi formula (YKY) has been clinically applied for the treatment of memory loss related disorders for more than 300 years with remarkable efficacy, but its pharmacological mechanism remains unclear. This study aimed to investigate the therapeutic effects of YKY on AD and its molecular mechanisms. We evaluated YKY's ameliorative effects on the AD phenotype in 3xTg-AD mice using the Morris water maze, histopathological staining, and immunofluorescence assays. The major chemical components of YKY were identified by UPLC-QTOF-MS/MS. Network pharmacology was employed to analyze the molecular mechanisms of YKY in treating AD, followed by validation of its regulatory effects on key pathways through immunofluorescence experiments and molecular docking. The results showed that YKY could significantly improve learning and memory ability, neuronal loss, β-amyloid deposition and glial cell activation in 3xTg-AD mice. 48 chemical components were identified from YKY, and network pharmacology analysis of them showed that YKY may improve AD by regulating apoptosis, PI3K/Akt and MAPK pathways. Immunofluorescence and molecular docking results also confirmed the regulatory effect of YKY on key targets of apoptosis, PI3K/Akt and p38 MAPK pathways. In conclusion, by integrating animal experiments and network pharmacology, the present study revealed the mechanism of YKY in inhibiting neuronal apoptosis by regulating PI3K/Akt and p38 MAPK pathways, which providing modern scientific evidence for the traditional clinical application of YKY.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"254"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961442","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":"Microglial pyroptosis in neurological disorders: mechanistic crosstalk, metabolic triggers, and therapeutic frontiers.","authors":"Reetesh Kumar, Siva Parsad Panda, Mosleh Mohammad Abomughaid, Sorabh Lakhanpal, D Avinash, Niraj Kumar Jha, Rohan Gupta","doi":"10.1007/s11011-025-01685-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01685-9","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) are characterized by the progressive decline of neuronal structure and function, with neuroinflammation and neuronal death as key pathogenic features. Pyroptosis, a highly inflammatory kind of programmed cell death (PCD) facilitated by gasdermin (GSDM) proteins and inflammasome activation, has garnered significant attention among new mechanisms. The increased expression of pyroptosis-related proteins, frequently co-localized with misfolded protein aggregates, indicates a crucial involvement in the advancement of different NDDs. Further, microglial pyroptosis exacerbates neuronal damage by hindering the removal of neurotoxic chemicals and intensifying inflammatory responses. Epigenetic and post-translational modifications (PTMs) of histone and non-histone proteins, along with metabolic dysregulation, significantly influence pyroptotic signaling, ultimately expediting neurodegeneration. Pyroptosis, owing to its pivotal involvement in inflammation and neuronal demise, is gaining recognition as a possible diagnostic and prognostic biomarker, particularly in the advancement of immunotherapeutic approaches. Herein, we thoroughly examine the molecular control of pyroptosis through PTMs and metabolic pathways, its implications for neurodegenerative and neuropsychiatric disorders, and recent therapeutic developments aimed at targeting pyroptotic pathways. It emphasizes the advancement of novel diagnostic instruments, such as genetic reporters and nanomaterial-based molecular probes for the real-time and non-invasive identification of pyroptotic activity. These discoveries establish a foundation for future tailored treatment strategies designed to alleviate pyroptosis-induced neuroinflammation and neurodegeneration. HIGHLIGHTS: 1. Pyroptosis is a pro-inflammatory cell death linked to neuroinflammatory conditions. 2. ROS and oxidative stress connect pyroptosis with other cell death mechanisms. 3. Altered glucose and lipid metabolism influence pyroptosis and neuronal degeneration. 4. PTMs of GSDMD, caspase-1, and ASC regulate pyroptosis in brain disorders. 5. Targeting microglial pyroptosis offers potential therapy for neurodegenerative diseases.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"251"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961483","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":"Targeting glucose transporters in parkinson's disease: a novel metabolic approach for disease modification.","authors":"Gursimran Singh, Shazia Ansari, Khadga Raj Aran","doi":"10.1007/s11011-025-01697-5","DOIUrl":"https://doi.org/10.1007/s11011-025-01697-5","url":null,"abstract":"<p><p>Glucose metabolism is vital for maintaining the effective functioning of the central nervous system (CNS). This energy supports synaptic activity, ion balance, and neurotransmitter synthesis, processes that depend on the GLUTs (glucose transporters), particularly GLUT1(Glucose transporter 1), GLUT2(Glucose transporter 2), and GLUT3 (Glucose transporter 3). There is growing evidence associating GLUT deficiency and metabolic disorders with neurodegenerative diseases, including Parkinson's disease (PD). PD is a progressive neurodegenerative disease linked with the degeneration of dopaminergic neurons in the SNpc, resulting in impaired motor and non-motor functions. More than 60% of patients with PD show glucose intolerance and insulin resistance, emphasizing the relation between metabolic disturbances and disease progression. The reduced expression of these GLUTs further restricts the neuronal glucose uptake, impairing ATP production and increasing liability to oxidative damage, leading to disease progression. Emerging finding suggests that targeting GLUT offers a therapeutic strategy for PD. Restoring GLUT function may help to reduce energy deficits and have neuroprotective effects. Several antidiabetic drugs have shown promise in reducing the symptoms and development of PD in both human and animal models. This narrative review addresses the current understanding of the connection between GLUT dysfunction and PD, highlighting the potential of targeting GLUT dysregulation as a novel therapeutic strategy. Additionally, repurposing antidiabetic drugs shows promise in improving insulin sensitivity and reducing neuroinflammation in PD. Addressing challenges like GLUT isoform specificity and BBB penetration provides a way for disease-modifying therapies that target GLUT dysfunction in PD, offering hope for effective management or reducing the rate of PD's progression.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"253"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961460","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}