Frontiers in Cellular Neuroscience最新文献

{"title":"Astrocyte regulation of behavioral outputs: the versatile roles of calcium.","authors":"Gillian Imrie, Isabella Farhy-Tselnicker","doi":"10.3389/fncel.2025.1606265","DOIUrl":"10.3389/fncel.2025.1606265","url":null,"abstract":"<p><p>Behavior arises from coordinated brain-wide neural and glial networks, enabling organisms to perceive, interpret, and respond to stimuli. Astrocytes play an important role in shaping behavioral output, yet the underlying molecular mechanisms are not fully understood. Astrocytes respond to intrinsic and extrinsic cues with calcium (Ca²⁺) fluctuations, which are highly heterogeneous across spatio-temporal scales, contexts, and brain regions. This heterogeneity allows astrocytes to exert dynamic regulatory effects on neuronal function but has made it challenging to understand the precise mechanisms and pathways linking astrocytic Ca²⁺ to specific behavioral outcomes, and the functional relevance of these signals remains unclear. Here, we review recent literature uncovering roles for astrocytic Ca²⁺ signaling in a wide array of behaviors, including cognitive, homeostatic, and affective focusing on its physiological roles, and potential pathological implications. We specifically highlight how different types of astrocytic Ca²⁺ signals are linked to distinct behavioral outcomes and discuss limitations and unanswered questions that remain to be addressed.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1606265"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181488","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 translational power of Alzheimer's-based organoid models in personalized medicine: an integrated biological and digital approach embodying patient clinical history.","authors":"Cristina Dolciotti, Marco Righi, Eleonora Grecu, Marcello Trucas, Cristina Maxia, Daniela Murtas, Andrea Diana","doi":"10.3389/fncel.2025.1553642","DOIUrl":"10.3389/fncel.2025.1553642","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by a multifaceted interplay of genetic, environmental, and pathological factors. Traditional diagnostic and research methods, including neuropsychological assessments, imaging, and cerebrospinal fluid (CSF) biomarkers, have advanced our understanding but remain limited by late-stage detection and challenges in modeling disease progression. The emergence of three-dimensional (3D) brain organoids (BOs) offers a transformative platform for bridging these gaps. BOs derived from patient-specific induced pluripotent stem cells (iPSCs) mimic the structural and functional complexities of the human brain. This advancement offers an alternative or complementary approach for studying AD pathology, including β-amyloid and tau protein aggregation, neuroinflammation, and aging processes. By integrating biological complexity with cutting-edge technological tools such as organ-on-a-chip systems, microelectrode arrays, and artificial intelligence-driven digital twins (DTs), it is hoped that BOs will facilitate real-time modeling of AD progression and response to interventions. These models capture central nervous system biomarkers and establish correlations with peripheral markers, fostering a holistic understanding of disease mechanisms. Furthermore, BOs provide a scalable and ethically sound alternative to animal models, advancing drug discovery and personalized therapeutic strategies. The convergence of BOs and DTs potentially represents a significant shift in AD research, enhancing predictive and preventive capacities through precise <i>in vitro</i> simulations of individual disease trajectories. This approach underscores the potential for personalized medicine, reducing the reliance on invasive diagnostics while promoting early intervention. As research progresses, integrating sporadic and familial AD models within this framework promises to refine our understanding of disease heterogeneity and drive innovations in treatment and care.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1553642"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181908","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":"Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration.","authors":"Olusola A Olatona, Sydney P Sterben, Sahan B S Kansakar, Aviva J Symes, Volha Liaudanskaya","doi":"10.3389/fncel.2025.1570596","DOIUrl":"10.3389/fncel.2025.1570596","url":null,"abstract":"<p><p>Mitochondria play a critical role in brain energy metabolism, cellular signaling, and homeostasis, making their dysfunction a key driver of secondary injury progression in traumatic brain injury (TBI). This review explores the relationship between mitochondrial bioenergetics, metabolism, oxidative stress, and neuroinflammation in the post-TBI brain. Mitochondrial dysfunction disrupts adenosine triphosphate (ATP) production, exacerbates calcium dysregulation, and generates reactive oxygen species, triggering a cascade of neuronal damage and neurodegenerative processes. Moreover, damaged mitochondria release damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), Cytochrome C, and ATP, triggering inflammatory pathways that amplify tissue injury. We discuss the metabolic shifts that occur post-TBI, including the transition from oxidative phosphorylation to glycolysis and the consequences of metabolic inflexibility. Potential therapeutic interventions targeting mitochondrial dynamics, bioenergetic support, and inflammation modulation are explored, highlighting emerging strategies such as mitochondrial-targeted antioxidants, metabolic substrate supplementation, and pharmacological regulators of mitochondrial permeability transition pores. Understanding these mechanisms is crucial for developing novel therapeutic approaches to mitigate neurodegeneration and enhance recovery following brain trauma.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1570596"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142022","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":"Neuroplastin 65 deficiency leads to the impairment of visual function through affecting ribbon synapse in retina of mice.","authors":"Jiu-Jiang Zeng, Ling Chen, Li-Fen Liu, Jia-Lu Wang, Jie Cheng, Ya-Ni Zheng, Lei Zhang, Xiao-Ming Zhang, Qiong-Lan Yuan","doi":"10.3389/fncel.2025.1558334","DOIUrl":"10.3389/fncel.2025.1558334","url":null,"abstract":"<p><p>Neuroplastin 65 (NP65) is a synapse-enriched glycoprotein in the central nervous system and is implicated in synaptic plasticity. In the present study, we found that NP65 knockout (NP65 KO) mice exhibit impaired visual function, including reductions in the amplitude of b-wave in scotopic flash electroretinogram (fERG), the amplitude of N1 and P1 waves in flash visual evoked potentials (fVEP), and the constriction rate in pupillary light reflexes (PLR). In wild-type (WT) mice, NP65 is specifically enriched in the synaptic ribbon (SR) of ribbon synapses labeled by Ribeye in the retina. We found that NP65 KO mice display nearly normal architecture of the retina. However, NP65 KO mice show a significant decrease in the immunoreactivity of presynaptic postsynaptic density protein 95 (PSD95), synaptophysin (SYN) and Ribeye in the outer plexiform layer (OPL). Moreover, the electron microscopy displays a decrease in synaptic ribbons and defects in postsynaptic structures in the ribbon synapses of the OPL in NP65 KO mice. In addition, we found that the apposition of presynaptic photoreceptor axonal terminals and postsynaptic bipolar cell dendrites in the OPL is misplaced in NP65 KO mice. Finally, we show that intravitreous injection of AAV-NP65 reverses the visual dysfunction, increases Ribeye expression and restores the normal arrangement in the OPL of NP65 KO mice. Together, our findings reveal that NP65 deficiency leads to visual function impairment by affecting ribbon synapses in the OPL of mice, suggesting that NP65 is critical for visual function in mammals and a potential target for degenerative retinopathy.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1558334"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127054","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":"GABAergic synaptic components are largely preserved across human and mouse neuronal models.","authors":"Beatriz Rebollo, Astghik Abrahamyan, Ulrich-Wilhelm Thomale, Angela M Kaindl, Melissa A Herman, Christian Rosenmund","doi":"10.3389/fncel.2025.1588894","DOIUrl":"10.3389/fncel.2025.1588894","url":null,"abstract":"<p><p>Synaptic transmission is essential for brain function. But which characteristics of synapse function are so crucial that they are conserved between species? In general, animal models have shaped our understanding of neuronal function, although in recent years our knowledge of human neurophysiology has vastly increased. Comparative analyses between rodent and human neurons have highlighted the similarities and differences in morpho-electrical features, but the extent to which the properties of neurotransmitter release are conserved is underexplored. In this study, we compared the intrinsic properties that determine synaptic strength in cultured GABAergic neurons from mouse and human. Our findings demonstrate that, while passive neuronal properties are different across species, synaptic properties are similar, suggesting that mechanisms of synaptic transmission are conserved between mouse and human neurons. This work provides valuable insight into the extent to which animal models reflect human synaptic components at the single cell level.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1588894"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092922","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":"Experience-dependent plasticity of multiple receptive field properties in lateral geniculate binocular neurons during the critical period.","authors":"Meng Pan, Jingjing Ye, Yijing Yan, Ailin Chen, Xinyu Li, Xin Jiang, Wei Wang, Xin Meng, Shujian Chen, Yu Gu, Xuefeng Shi","doi":"10.3389/fncel.2025.1574505","DOIUrl":"https://doi.org/10.3389/fncel.2025.1574505","url":null,"abstract":"<p><p>The visual thalamus serves as a critical hub for feature preprocessing in visual processing pathways. Emerging evidence demonstrates that experience-dependent plasticity can be revealed by monocular deprivation (MD) in the dorsolateral geniculate nucleus (dLGN) of the thalamus. However, whether and how this thalamic plasticity induces changes in multiple receptive field properties and the potential mechanisms remain unclear. Using <i>in vivo</i> electrophysiology, here we show that binocular neurons in the dLGN of 4-day MD mice starting at P28 undergo a significant ocular dominance (OD) shift during the critical period. This OD plasticity could be attributed to the potentiation of ipsilateral eye responses but not to the depression of deprived eye responses, contrasting with conventional observations in the primary visual cortex (V1). The direction and orientation selectivity of ipsilateral eye responses, but not of contralateral eye responses in these neurons, were dramatically reduced. Developmental analysis revealed pre-critical and critical period-associated changes in densities of both GABA positive neurons and GABA_A receptor α1 subunit (GABRA1) positive neurons. However, early compensatory inhibition from V1 feedback in P18 MD mice maintained network stability with no changes in OD and feature selectivity. Mechanistically, pharmacological activation of GABA_A receptors rescued the MD-induced OD shifts and feature selectivity impairments in critical period MD mice, operating independently of the V1 feedback. Furthermore, under different contrast levels and spatial frequencies, these critical period-associated changes in receptive field properties still indicate alterations in ipsilateral eye responses alone. Together, these findings provide novel insights into the developmental mechanisms of thalamic sensory processing, highlighting the thalamus as an active participant in experience-dependent visual plasticity rather than merely a passive relay station. The identified GABA-mediated plasticity mechanisms offer potential therapeutic targets for visual system disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1574505"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992104","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 wave nature of the action potential.","authors":"Vitaly L Galinsky, Lawrence R Frank","doi":"10.3389/fncel.2025.1467466","DOIUrl":"https://doi.org/10.3389/fncel.2025.1467466","url":null,"abstract":"<p><p>An alternative to the standard Hodgkin-Huxley model for the action potential in axons is presented. It is based on our recently developed theory of electric field wave propagation in anisotropic and inhomogeneous brain tissues, which has been shown to explain a broad range of observed coherent synchronous brain electrical processes. We demonstrate that this theory also explains the spiking behavior of single neurons, thereby bridging the gap between the fundamental element of brain electrical activity-the neuron-and large-scale coherent synchronous electrical activity. We demonstrate that our recently developed theory of electric field wave propagation in anisotropic and inhomogeneous brain tissues, which has been shown to explain a broad range of observed coherent synchronous brain electrical processes, also applies to the spiking behavior of single neurons, thus bridging the gap between the fundamental element of brain electrical activity (the neuron) and large-scale coherent synchronous electrical activity. Our analysis indicates that a non-linear system with several small parameters can mathematically describe the membrane interface of the axonal cellular system. This enables the rigorous derivation of an accurate yet simpler non-linear model through the formal small-parameter expansion. The resulting action potential model exhibits a smooth, continuous transition from the linear wave oscillatory regime to the non-linear spiking regime, as well as a critical transition to a non-oscillatory regime. These transitions occur with changes in the criticality parameter and include several different bifurcation types, representative of the various experimentally detected neuron types. This new theory addresses the limitations of the Hodgkin-Huxley model, including its inability to explain extracellular spiking, efficient brain synchronization, saltatory conduction along myelinated axons, and various other observed coherent macroscopic brain electrical phenomena. We also demonstrate that our approach recovers the standard cable axon theory, utilizing the relatively simple assumptions of piece-wise homogeneity and isotropy. However, the diffusion process described by the cable equation is not capable of supporting action potential propagation across a wide range of experimentally reported axon parameters.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1467466"},"PeriodicalIF":4.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986327","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":"Decoding serotonin: the molecular symphony behind depression.","authors":"Yue Shu, Lei Tian, Xing Wang, Tinyang Meng, Shouyang Yu, Yulan Li","doi":"10.3389/fncel.2025.1572462","DOIUrl":"https://doi.org/10.3389/fncel.2025.1572462","url":null,"abstract":"<p><p>The serotonin (5-hydroxytryptamine) system represents a crucial neurotransmitter network that regulates mood, behavior, and cognitive functions, playing a significant role in the pathogenesis and progression of depression. Although this perspective faces significant challenges, the serotonin system continues to exert substantial modulatory effects on specific aspects of psychological functioning and actively contributes to multiple pathological processes in depression development. Therefore, this review systematically integrates interdisciplinary research advances regarding the relationship between the 5-hydroxytryptamine (5-HT) system and depression. By focusing on core biological processes including serotonin biosynthesis and metabolism, SERT gene regulatory networks, and protein molecular modifications, it aims to elucidate how 5-HT system dysregulation contributes to the development of depression, while providing novel research perspectives and therapeutic targets for innovative antidepressant drug development.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1572462"},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007103","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":"Circulating CD4+, CD8+, and double-negative T cells in ischemic stroke and stroke-associated infection: a prospective case-control study.","authors":"Magdalena Telec, Magdalena Frydrychowicz, Radosław Kazmierski, Izabela Wojtasz, Grzegorz Dworacki, Wojciech Kozubski, Maria Łukasik","doi":"10.3389/fncel.2025.1547905","DOIUrl":"https://doi.org/10.3389/fncel.2025.1547905","url":null,"abstract":"<p><strong>Introduction: </strong>Adaptive immunity after a stroke results in a shift of T cells between compartments, leading to peripheral lymphopenia and an increased number of T cells within the brain lesion. Stroke-associated infection (SAI) presents a clinically significant challenge in stroke units. The role of T-cell subsets in the post-stroke immune response and in SAI remains unclear. Thus, we aimed to observe the quantitative changes of circulating CD4+, CD8+, double-negative T cells, and the CD4+/CD8+ ratio in stroke and SAI.</p><p><strong>Methods: </strong>We prospectively assessed circulating CD4+, CD8+, and double-negative T cells using flow cytometry in 52 patients on days 1, 3, 10, and 90 after ischemic stroke. We compared the results to those obtained from age-, sex-, and vascular risk factor-matched controls. We analyzed lymphocyte parameters in relation to clinical outcome, SAI, infarct lesion volume, and risk factor burden.</p><p><strong>Results: </strong>There were no differences in the studied parameters between stroke patients and controls, as well as between subjects with and without SAI. A higher percentage of CD4+ T cells and a higher CD4+/CD8+ ratio correlated with better clinical status in the acute and subacute phases, while CD8+ T cells showed the opposite correlation. The percentage of CD8+ T cells positively correlated with CRP levels during the acute and subacute phases of stroke, as well as in the control group. A negative correlation was noted between the percentage of CD4+ T cells on D1 and the serum CRP level on D10 after stroke. Similarly, the CD4+/CD8+ ratio on D1 negatively correlated with CRP on D1, D3, and D10. In patients with a history of hypertension (HT), there was a higher percentage of CD8+ T cells and a lower percentage of CD4+ T cells in the acute phase of stroke than those without HT.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1547905"},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975650","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":"O⁶-methylguanine DNA methyltransferase (MGMT) expression in U1242 glioblastoma cells enhances <i>in vitro</i> clonogenicity, tumor implantation <i>in vivo</i>, and sensitivity to alisertib-carboplatin combination treatment.","authors":"Müge Sak, Brian J Williams, Andrew J Hey, Mayur Sharma, Leslie Schier, Megan J Wilson, Mahatma Ortega, Alyssa I Lara, Mikaela N Brentlinger, Norman L Lehman","doi":"10.3389/fncel.2025.1552015","DOIUrl":"10.3389/fncel.2025.1552015","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common and aggressive primary adult CNS tumor. Increased understanding of glioma biology is needed for novel treatment strategies and maximization of current therapies. The action of the widely used antiglioma drug, temozolomide (TMZ), relies on its ability to methylate DNA guanine bases leading to DNA double strand breaks and apoptosis. However, glioma cells capable of reversing guanine methylation via the repair enzyme <i>O</i> ⁶-methylguanine DNA methyltransferase (MGMT) are resistant to TMZ. GBMs exhibiting high MGMT expression, reflected by MGMT gene promoter hypomethylation, respond poorly to both chemo- and radiation therapy. To investigate possible non-canonical biological effects of MGMT and develop a tool to investigate drug sensitivity and resistance, we generated MGMT knockout (KO) U1242 GBM cells. MGMT KO U1242 cells showed substantially increased sensitivity to TMZ <i>in vivo</i>, and unlike wildtype U1242 cells, failed to form tumors in nude mouse brains. They also showed reduced growth in soft agar, as did wildtype U1242 and additional glioma cell lines in which MGMT expression was knocked down by siRNA. MGMT thus possesses cellular functions related to tumor cell engraftment and anchorage-independent growth beyond guanine methyltransferase repair. We additionally show that the combination of the AURKA inhibitor alisertib and carboplatin selectively induces apoptosis in high MGMT expressing wildtype U1242 cells versus MGMT KO U1242 cells and extends survival of mice orthotopically implanted with wildtype U1242 cells. This or other platinum-based drug combinations may represent a potentially effective treatment approach to chemotherapy for GBM with MGMT promoter hypomethylation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1552015"},"PeriodicalIF":4.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967232","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}