Molecular Neurobiology最新文献

{"title":"The Antioxidative, Anti-inflammatory and Anti-apoptotic Effects of Tetrapleura Tetraptera (Aidan) Ethanol Leaf Extract in the Brain of Wistar Rats Exposed to Aspartame.","authors":"Akeem Olalekan Lawal, Olaoluwa Oladimeji Agboola, Moses Orimoloye Akinjiyan, Taiwo Tolulope Ijatuyi, Damilola Timothy Dahunsi, Oritoke Modupe Okeowo, Ibukun Mary Folorunso, Olakunle Julius Olajuyigbe, Olusola Olalekan Elekofehinti","doi":"10.1007/s12035-025-04839-z","DOIUrl":"10.1007/s12035-025-04839-z","url":null,"abstract":"<p><p>Artificial sweeteners' neurotoxicity remains a significant health concern. This study investigated the neurotoxic effects of aspartame (ASP) and evaluated the neuroprotective potential of Tetrapleura tetraptera ethanol extract (TT) in Wistar rats. Thirty male rats were grouped into six (n = 5) and some received oral ASP administration for 14 days, with some groups post-treated with TT (200 and 400 mg/kg) orally for 14 days. Neurotransmitter function, oxidative stress markers, inflammatory mediators, and apoptotic parameters were assessed using biochemical assays and RT-PCR on serum and brain tissues after the sacrifice. ASP significantly (p < 0.001) increased AChE and BChE activities while decreasing dopamine levels. RT-PCR analysis revealed that ASP upregulated pro-inflammatory genes (TNF-α, IL-6, IL-1β) and pro-apoptotic markers (BAX, CASP3, CASP9, P53) while downregulating anti-apoptotic BCL-2 gene expression. ASP also reduced antioxidant levels (GSH, GCL), elevated S100B level and activated cAMP/PKA signalling. TT post-treatment significantly (p < 0.001) reversed these alterations, reducing MDA and GSSG levels while enhancing GSH/GSSG ratio and antioxidant activities. TT markedly downregulated inflammatory markers and upregulated IL-10 expression. Histopathological examination suggests TT's protective effects against ASP-induced neural damage. These findings indicate that TT exhibits neuroprotective properties through its antioxidant, anti-inflammatory, and anti-apoptotic activities against ASP-induced neurotoxicity.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9430-9448"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Key Fatty Acid Metabolism-Related Genes in Alzheimer's Disease.","authors":"Bo Yan, Pan Liao, Wei Zhang, Zhaoli Han, Conglin Wang, Fanglian Chen, Ping Lei","doi":"10.1007/s12035-025-04857-x","DOIUrl":"10.1007/s12035-025-04857-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and the role of fatty acid metabolism in its pathogenesis remains incompletely understood. Using AD transcriptome sequencing data from the GEO database, we initially screened for differentially expressed genes and applied Weighted Gene Correlation Network Analysis (WGCNA) to identify crucial gene modules. By intersecting these genes with fatty acid metabolism-related genes (FAMRGs), we obtained AD-related fatty acid metabolism genes (AD-FAMRGs). Subsequently, we conducted KEGG, GO, and Single-sample Gene Set Enrichment Analysis (ssGSEA). Furthermore, we employed three machine learning algorithms to determine the key AD-FAMRGs. Risk genes were thus identified, leading to the construction of a risk model which was subsequently validated through receiver operating characteristic (ROC) curve analysis. Additionally, protein docking studies were performed to assess interactions between key AD-FAMRGs and Tau as well as amyloid beta (Aβ) proteins. To explore potential therapeutic avenues, we searched the DrugBank database for agents targeting these AD-FAMRGs, followed by molecular docking and dynamics simulations. Our investigations highlighted three key AD-FAMRGs: DLD, ELOVL5, and HMGCS1. Functional enrichment analysis indicated their association with metabolism, oxidative stress, and AD pathogenesis. ZDOCK analysis further suggested their interactions with Tau and Aβ proteins, pointing to their possible involvement in AD's pathological processes. ROC analysis demonstrated the predictive accuracy of these AD-FAMRGs, with AUC values ranging from 0.764 to 0.876. Molecular docking and dynamic simulations confirmed the favorable binding of predicted therapeutic agents to these key AD-FAMRGs. Our findings suggest that fatty acid metabolism may be involved in AD pathogenesis, and DLD, ELOVL5, and HMGCS1 may serve as potential therapeutic targets for AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9399-9415"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversing Neuronal Klotho Dysfunction-Mediated Diabetic Neuropathy Through 16:8 Intermittent Fasting.","authors":"Ying-Shuang Chang, Yu-Yu Kan, Tzu-Ning Chao, Yi-Hsuan Chen, Yu-Lin Hsieh","doi":"10.1007/s12035-025-04849-x","DOIUrl":"10.1007/s12035-025-04849-x","url":null,"abstract":"<p><p>Insulin supply is the golden standard for type 1 diabetes mellitus (T1DM) therapy. Is there a drug-reduction application for reversing glucose metabolism disabled and diabetic neuropathy (DN), and is it suitable for the young and elderly populations? Reducing T1DM-associated DN, and maintaining glucose metabolism require using the anti-aging gene Klotho to regulate specific signaling cascades. This study applied five 16:8 intermittent fasting (16-h fasting, 8-h eating; 168if) protocols by different executing times to young and elderly diabetic mice to evaluate whether 168if is age-dependent and how it alters Klotho-related signaling molecules. Blood glucose levels were efficiently reduced when 168if was implemented in the early stage of T1DM onset (DNf group) of young and elderly mice. Another four groups failed to reduce blood sugar. However, the DNf protocol was unsuitable for diabetic elderly mice because it posed a higher mortality risk for this population. Young DNf mice exhibited reduced thermal hyperalgesia and mechanical allodynia and reversed Klotho downregulation and protein kinase C epsilon (PKCε) upregulation compared with DN mice. Furthermore, young DNf mice exhibited normalization of fibroblast growth factor receptor 1 (FGFR1) and nuclear factor κB (NF-κB) expression, which is involved in Klotho-related glucose metabolism and anti-inflammation. The expression densities of PKCε, Klotho, FGFR1, and NF-κB were linear to neuropathic manifestations. This study demonstrated the effectiveness of 168if application in the early stage of T1DM onset, a straightforward and convenient dietary control method, as a blood glucose control for achieving pharmaceutical reduction and relieving neuropathic pain in young T1DM patients.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9483-9496"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacology and Neuroprotective Effects of Gingerol in Alzheimer's Disease.","authors":"Sakthi Priyadarshini, Keshav Goyal, Roopashree R, Saurabh Gupta, Aatreyi Roy, Ritabrata Biswas, Sandeep Patra, Payal Chauhan, Karan Wadhwa, Govind Singh, Mehnaz Kamal, Danish Iqbal, Mohammed Alsaweed, Mohana Vamsi Nuli, Mosleh Mohammad Abomughaid, Abdulmajeed G Almutary, Jitendra Kumar Sinha, Pooja Bansal, Bindu Rani, Chakshu Walia, G V Sivaprasad, Shreesh Ojha, Vinod Kumar Nelson, Niraj Kumar Jha","doi":"10.1007/s12035-024-04484-y","DOIUrl":"10.1007/s12035-024-04484-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition that results in brain shrinkage and the death of brain cells. The search for new treatment agents with many targets is now crucial due to the insufficient effectiveness, and adverse effects, including pharmacokinetic issues of traditional AD medications. Although phytochemicals have anti-disease characteristics and thus are widely used and accepted by people, researchers have also determined some of their most beneficial functions. Sesquiterpenes, volatile oils, and aromatic ketones (gingerols) are abundant in ginger. The most pharmacologically active components of ginger are considered to be gingerols. These gingerols are the compounds that impart spicy characteristics to the plant. Besides, gingerols readily undergo dehydration and produce another class of compounds, shogaols. These gingerols, shogaols, and other compounds, like zingerone, are mainly responsible for their distinctive aroma and pharmacological effects. This review aims to delineate the therapeutic potentials of gingerol in different AD models by assessing available literature reporting its effect on various cellular and molecular pathways. Although ginger is well recognized as a non-toxic nutraceutical, existing clinical research lacks robust evidence to support its efficacy in treating NDs, including AD. Clinical studies did not provide sufficient data that supports its use in treating various NDs including AD. Therefore, further research is essential to establish the safety and effectiveness of ginger and its constituents, ultimately paving the way for its development as a potential therapeutic agent for AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8166-8186"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromodulation of Dopamine D2 Receptors Alters Orbitofrontal Neuronal Activity and Reduces Risk-Prone Behavior in Male Rats with Inflammatory Pain.","authors":"Margarida Dourado, Helder Cardoso-Cruz, Clara Monteiro, Vasco Galhardo","doi":"10.1007/s12035-025-04781-0","DOIUrl":"10.1007/s12035-025-04781-0","url":null,"abstract":"<p><p>Dopamine (DA) is believed to play a crucial role in maintaining the integrity of the rodent orbitofrontal cortex (OFC) networks during risk-based decision-making processes. Chronic pain conditions can lead to impaired DAergic signaling, which, in turn, may affect the motivational control of risk-based responses. Nevertheless, the neural mechanisms underlying this instability are poorly understood. In this study, we aimed to investigate whether this impairment is dependent on the activity of the DA D2 receptor (D2r). To address this hypothesis, we implanted bilateral matrices of multielectrodes into the OFC of male rats and recorded the neural activity while they performed a food-reinforced rodent gambling task (rGT). We evaluated behavioral performance and neural activity patterns before and after inducing a model of inflammatory pain - complete Freund's adjuvant (CFA) model. Our findings revealed that rats treated with CFA exhibited an abnormal preference for the large/uncertain reward during rGT performance. This altered behavioral choice profile could be reversed by prior systemic administration of D2r ligands (0.05 mg/kg, quinpirole or raclopride), indicating a potential role of D2r in the decision-making process required for this task. The administration of these ligands at the specified dosages did not affect pain responses, but lead to a significant alteration of OFC neuronal activity that support goal-directed choice responses in the rGT. Finally, we found evidence that CFA-treated rats exhibit OFC functional changes, namely an upregulation of DA D1 receptor (D1r) and a downregulation of DA beta-hydroxylase (DH). These results demonstrate that the disruption of DAergic balance in the brain networks is crucial for the development of high-risk decision profiles during painful conditions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8187-8203"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Risks of Minoxidil in Pheochromocytoma and Paraganglioma: A Commentary on Safety Concerns and Mechanisms.","authors":"Emirhan Harbi, Ozcan Yildiz, Michael Aschner","doi":"10.1007/s12035-025-04842-4","DOIUrl":"10.1007/s12035-025-04842-4","url":null,"abstract":"<p><p>Pheochromocytoma and paraganglioma are neuroendocrine tumours characterised by excessive catecholamine release. Minoxidil, a potent vasodilator commonly used for hypertension and androgenetic alopecia, may exacerbate cardiovascular complications associated with pheochromocytoma due to its mechanisms-of-action. This commentary aims to elucidate the potential risks and safety concerns associated with the use of minoxidil in patients with pheochromocytoma. Here, we discuss the need for careful prescribing practices when considering minoxidil in pheochromocytoma-associated hypertension and the potential problems that minoxidil use may cause in pheochromocytoma patients.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9170-9174"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Crocin's Role in Alleviating Memory Impairments and Depression-like Behaviors Induced by REM Sleep Deprivation, Focusing on BDNF and GSK-3β in Male Rats.","authors":"Golbahar Lotfi, Maryam Eslami, Mahdieh Gholami, Salar Vaseghi, Batool Ghorbani Yekta","doi":"10.1007/s12035-025-04753-4","DOIUrl":"10.1007/s12035-025-04753-4","url":null,"abstract":"<p><p>Rapid-eye movement sleep deprivation (REM SD) drastically alters behavioral functions and the mood state. Evidence demonstrates that the effects of REM SD on cognition and mood vary significantly based on the duration of deprivation. On the other hand, crocin (as a natural therapeutic compound found in Saffron) may be beneficial for the alleviation of SD effect. The present research aimed to explore the effects of REM SD of varying durations on behavioral functions and the expression levels of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 beta (GSK-3β) in the prefrontal cortex. REM SD was conducted for 1, 5, or 10 days (6 h per day). Crocin was injected intraperitoneally at the dose of 50 mg/kg. The results showed that REM SD for 5- and 10-days increased locomotor activity and rearing, decreased pain threshold, and impaired passive avoidance memory performance. REM SD for 5- and 10-days increased the expression levels of GSK-3β, while only REM SD for 5 days decreased BDNF levels. Crocin (only in rats exposed to REM SD for 5 days) restored behavioral alterations, while in rats exposed to REM SD for 10 days had no effect. Interestingly, crocin in rats exposed to REM SD for 5- and 10-days attenuated GSK-3β upregulation. In addition, crocin in rats exposed to REM SD for 5 but not 10 days attenuated BDNF down regulation. In conclusion, the duration of REM SD is a crucial determinant of its impact on cognitive and mood functions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8638-8651"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise Ameliorates Dysregulated Mitochondrial Fission, Mitochondrial Respiration, and Neuronal Apoptosis in Parkinson's Disease Mice via the Irisin/AMPK/SIRT1 Pathway.","authors":"Nan Li, Bin Wang, Yuanxin Wang, Xin Tian, Junjie Lin, Xun Sun, Yu Sun, Xin Zhang, Haocheng Xu, Mingzhi Li, Fanxi Zeng, Renqing Zhao","doi":"10.1007/s12035-025-04801-z","DOIUrl":"10.1007/s12035-025-04801-z","url":null,"abstract":"<p><p>Mitochondrial dysfunction plays a crucial role in the pathogenesis of Parkinson's disease (PD), yet therapeutic strategies targeting mitochondrial function remain limited. Exercise has shown neuroprotective benefits in PD, but the underlying mechanisms are not fully understood. This study aimed to investigate how exercise affects MPTP-induced excessive apoptosis, mitochondrial fission, and mitochondrial function in PD mice, with a focus on the Irisin/AMPK/SIRT1 pathway. Thirty-two male C57BL/6 J mice, aged 7-8 weeks, were randomly assigned to control (n = 8) and experimental groups (n = 24). Mice in the experimental groups were administered intraperitoneal injections of MPTP to induce the PD model. Subsequently, the experimental mice were divided into three groups (8 mice in each group): the sedentary group (PD), the group subjected to 10 weeks of treadmill exercise (PDEX), and the group receiving both treadmill exercise and Irisin antagonist injections (EXRG). Upon completion of the 10-week intervention, behavioral assessments were performed. Following this, the mice were euthanized to collect brain samples and subjected to immunohistochemistry, immunofluorescence, ELISA, citrate synthase assay, and Western blot analyses. MPTP-treated mice exhibited significant motor dysfunction and dopaminergic neuron loss in the nigrostriatal regions, which were alleviated after a 10-week exercise intervention. Exercise significantly reduced MPTP-induced neuronal apoptosis, as evidenced by decreased cellular debris and abnormal nuclear morphology, increased Bcl-2 protein levels, and decreased BAX expression. Furthermore, exercise mitigated abnormal mitochondrial fission in PD mice and improved mitochondrial function-related markers. This was reflected by reduced immunohistochemical signals and protein expression levels of Drp1, Fis1, and MFF, as well as increased citrate synthase activity and elevated expression levels of COX-I and COX-IV. In the substantia nigra of PD mice, the expression levels of Irisin, p-AMPK, and SIRT1 were reduced but were notably elevated after the 10-week exercise intervention. However, chronic treatment with Cyclo RGDyk to block Irisin signaling potentially counteracted the exercise-induced increases in p-AMPK and Sirt1 expression. Moreover, blocking the Irisin signaling pathway reversed the beneficial effects of exercise on mitochondrial fission, mitochondrial function, and neuronal apoptosis. Exercise is an effective approach for alleviating PD pathology by reducing excessive mitochondrial fission, dysregulated mitochondrial respiration and metabolism, and neuronal loss. The neuroprotective effects of exercise are achieved, in part, by regulating the Irisin/AMPK/SIRT1 signaling pathway. This study underscores the potential of targeting Irisin signaling as a therapeutic strategy of exercise to enhance mitochondrial function and promote neuronal survival in PD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8843-8856"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Nexus: How Ferroptosis, Microglia, and Neuroinflammation Converge in Ischemic Stroke Pathogenesis.","authors":"Zhiyan Liu, Xueyang Shen, Mingming Li, Pei Liu, Zhaoming Ge, Jing Jin","doi":"10.1007/s12035-025-04815-7","DOIUrl":"10.1007/s12035-025-04815-7","url":null,"abstract":"<p><p>Ischemic stroke ranks as a leading cause of significant morbidity, mortality, and disability globally, with currently available therapeutic options remaining constrained. Prior research has elucidated that neuroinflammatory processes and pronounced microglial activation constitute critical underpinnings of ischemic stroke, precipitating neural system dysfunctions and facilitating disease exacerbation. Ferroptosis, an emergent paradigm, plays a pivotal role in this context. Defined by an iron-dependent cell death pathway, ferroptosis is distinguished by marked iron accumulation, lipid peroxidation, and the concomitant irreversible destruction of the plasma membrane, thereby contributing to the propagation of ischemic stroke through the accelerated neuronal dysfunction and aberrant microglial activation. Within this review, we initially delineate the constructs of ferroptosis, microglia, ischemic stroke, and their interconnections. Subsequently, we delve into the quintessential involvement of ferroptosis in the aberrant microglial activation associated with ischemic stroke's neuroinflammatory milieu, paving the path for the exploration of novel potential therapeutic targets against ischemic stroke.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8965-8976"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Investigation of Neurotrophic trans-Banglene Reveals Potential Link to Iron Homeostasis.","authors":"Piyumi B Wijesiri Gunawardana, Khyati Gohil, Kyung-Mee Moon, Leonard J Foster, Florence J Williams","doi":"10.1007/s12035-025-04772-1","DOIUrl":"10.1007/s12035-025-04772-1","url":null,"abstract":"<p><p>In an effort to gain insight into cellular systems impacted by neurotrophic trans-banglene (t-BG), global proteomic profiling and Western blot analyses were employed. Expression level changes in response to t-BG treatment were compared to those observed with nerve growth factor (NGF), a natural neurotrophic protein and functional analog to t-BG. Findings from these studies did not point to direct interception of NGF/TrkA signaling by t-BG. Instead, significant alterations in iron-binding and iron-regulating proteins were observed. While total iron levels showed no change across all treatments, intracellular iron measurements and mitochondrial iron measurements demonstrated lower ferrous (Fe²⁺) ion levels in t-BG treated cells but not in NGF treated cells. These results highlight a potential connection between iron regulation and neurotrophic activity, a relationship which has, to date, not been well studied. These results are also notable given that iron dysregulation occurs in most neurodegenerative disease settings, and that iron has been shown to facilitate protein aggregation and apoptotic mechanisms.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9031-9051"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}