Neurobiology of Disease最新文献

{"title":"A role for the autophagy receptor NBR1 in the degradation of tau aggregates","authors":"Marie Neu ,&nbsp;Iwan Parfentev ,&nbsp;Gregory K. Potts ,&nbsp;Nina Stöberl ,&nbsp;Jürgen Korffmann ,&nbsp;Andreas Striebinger ,&nbsp;Daniela Geist ,&nbsp;Dimitris Papageorgiou ,&nbsp;Hanna Tarhonskaya ,&nbsp;Nicholas McKitterick ,&nbsp;Jeroen van Bergeijk ,&nbsp;Christopher Untucht ,&nbsp;Peter Reinhardt ,&nbsp;Jon D. Williams ,&nbsp;Michaela J. Heimann ,&nbsp;Laura Gasparini ,&nbsp;Dagmar E. Ehrnhoefer","doi":"10.1016/j.nbd.2025.107060","DOIUrl":"10.1016/j.nbd.2025.107060","url":null,"abstract":"<div><div>Neurofibrillary tangles (NFTs), comprising hyperphosphorylated and aggregated Tau protein, are a primary neuropathological feature of Alzheimer's Disease (AD). In patients, the formation and spread of NFTs across the brain correlate with cognitive decline. However, the mechanisms driving Tau aggregation and leading to the subsequent neuronal dysfunction are not fully understood. In this study, we explored proteomic and phosphoproteomic changes resulting from the seed-induced aggregation of endogenous Tau in human neurons, derived from induced pluripotent stem cells (iPSCs). We discovered previously undescribed phosphorylation sites on NBR1, an autophagy receptor, which were significantly altered by Tau aggregation <em>in vitro</em>. We further show that NBR1 directly interacts with phosphorylated Tau and Tau aggregates in various cellular models. This interaction is associated with autophagic Tau degradation in HEK biosensor cells, and siRNA-mediated knockdown of NBR1 significantly increases Tau aggregate levels in iPSC-derived neurons. Additionally, we find that NBR1 expression is significantly increased in AD patients, and it specifically interacts with Tau in human AD brain, underscoring the relevance of our findings to the human disease. These insights provide a deeper understanding of the molecular interactions between autophagy receptors and Tau pathology in AD and reveal a role for NBR1 as an important receptor for pathological forms of Tau.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107060"},"PeriodicalIF":5.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862341","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":"Alpha-synuclein inclusions reduced by PIKfyve inhibition in Parkinson disease cell models","authors":"Sara Lucas-Del-Pozo ,&nbsp;Giuseppe Uras ,&nbsp;Federico Fierli ,&nbsp;Veronica Lentini ,&nbsp;Sofia Koletsi ,&nbsp;Carlos Lazaro-Hernandez ,&nbsp;Kai-Yin Chau ,&nbsp;Derralynn A. Hughes ,&nbsp;Anthony H.V. Schapira","doi":"10.1016/j.nbd.2025.107053","DOIUrl":"10.1016/j.nbd.2025.107053","url":null,"abstract":"<div><h3>Objective</h3><div>Parkinson's disease (PD) pathophysiology is associated with a progressive loss of dopaminergic neurons in the substantia nigra and accumulation of insoluble inclusions of misfolded alpha-synuclein. In this study, we used a neuroblastoma-derived cell model overexpressing a pro-aggregation form of alpha-synuclein and human-derived induced-pluripotent stem cells (iPSCs) to investigate the efficacy of PIKfyve-mediated lysosomal biogenesis to reduce alpha-synuclein inclusions.</div></div><div><h3>Methods</h3><div>We used high-content imaging and enzymatic assays to follow the progression of lysosomal biogenesis, lysosomal catabolism and alpha-synuclein accumulation. The cell models used recapitulated important elements of the biochemical phenotype observed in PD dopaminergic neurons, including alpha-synuclein inclusions and impaired glucocerebrosidase.</div></div><div><h3>Results</h3><div>PIKfyve inhibition by YM201636 resulted in a lysosomal-dependant reduction of alpha-synuclein inclusions as early as 24 h post-treatment. YM201636 induced an increase in nuclear translocation of TFEB, and an increase in lysosomal markers LAMP1 and HEXA. PIKfyve-inhibition was also tested in neuronal-differentiated neuroblastoma-derived cells and iPSCs-derived dopaminergic neurons. In these cells, YM201636 substantially reduced alpha-synuclein inclusions and increased TFEB nuclear localisation.</div></div><div><h3>Conclusion</h3><div>These findings suggest that PIKfyve signalling pathways could represent a therapeutic target to reduce alpha-synuclein in PD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107053"},"PeriodicalIF":5.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855873","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":"Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice","authors":"Chu-han Liu ,&nbsp;Hui-jie Feng ,&nbsp;Fei Peng ,&nbsp;Shan Wang ,&nbsp;Liu-jie Zhao ,&nbsp;Hui Zhu ,&nbsp;Xue-ying Dou ,&nbsp;Ting Yuan ,&nbsp;Chuang Li ,&nbsp;Nan Zhou ,&nbsp;Wen-xin Zhang ,&nbsp;Xuan-ren Wang ,&nbsp;Yu-lin Dong","doi":"10.1016/j.nbd.2025.107056","DOIUrl":"10.1016/j.nbd.2025.107056","url":null,"abstract":"<div><div>The mediodorsal thalamus (MD) constitutes an integral component of the medial nociceptive transmission system, although its precise role and related neural pathway in pain processing remains incompletely elucidated. While anatomical studies have confirm reciprocal projections between the MD and anterior cingulate cortex (ACC), the functional contribution of ACC-MD neural circuitry to nociceptive regulation has not yet been systematically investigated. In this study, we used immunohistochemistry, pharmacogenetic manipulations, and multidimensional behavioral assessments to investigate the role of the MD and ACC-MD pathway in pain modulation. The MD can be activated by nociceptive stimuli, and mediates both exteroception-evoked reflexive-defensive reactions and interoception-mediated self-caring responses. Chemogenetics activation of the MD or the ACC-MD pathway induced hyperalgesia alongside aversion and anxiety-like behaviors. While inhibiting both alleviates pain and emotional comorbidities in neuropathic pain mice. These results identify a cortico-thalamic descending pathway that facilitates pain and emotional comorbidity, providing mechanistic insights for the developing neuromodulaion-based therapies against refractory neuropathic pain.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107056"},"PeriodicalIF":5.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855874","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":"Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis","authors":"Xiarong Gong ,&nbsp;Wei Li ,&nbsp;Chengsi Luo ,&nbsp;Yanghua Tian ,&nbsp;Jiaojian Wang ,&nbsp;Yuan Gao ,&nbsp;Yuanyuan Guo ,&nbsp;Meiling Chen ,&nbsp;Qiang Meng","doi":"10.1016/j.nbd.2025.107050","DOIUrl":"10.1016/j.nbd.2025.107050","url":null,"abstract":"<div><h3>Aims</h3><div>Anti-<em>N</em>-methyl-<span>d</span>-aspartate (Anti-NMDA) receptor encephalitis is characterized by widespread neural dysfunction, yet the underlying neurochemical and molecular mechanisms remain poorly understood. This study aimed to investigate whether functional alterations in anti-NMDAR encephalitis are spatially associated with neurotransmitter receptor distributions and transcriptomic profiles, to uncover their neurochemical, molecular, and cellular signatures.</div></div><div><h3>Methods</h3><div>A total of 25 patients diagnosed with anti-NMDA receptor encephalitis and 30 healthy controls (HCs) were recruited in this study. All participants underwent resting-state functional MRI (rs-fMRI) scanning, with patients being scanned during the recovery phase of the disease. To explore the neurochemical, molecular and cellular signatures underlying altered brain functional activity, we conducted neuroimaging-neurotransmitter, neuroimaging-transcriptome regression analyses and cell type enrichment analysis, linking aberrant fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) patterns with PET-derived receptor maps and transcriptomic profiles from the Allen Human Brain Atlas (AHBA).</div></div><div><h3>Results</h3><div>Patients exhibited significant alterations in fALFF/ReHo across the frontal, temporal, and occipital cortices. Neuroimaging-neurotransmitter regression analyses revealed that these functional abnormalities were significantly associated with neurotransmitter receptor maps, particularly involving serotonin (5-HT2a) and dopamine (D1) systems. Neuroimaging–transcriptome regression analyses further demonstrated that the genes associated with fALFF/ReHo alterations were primarily enriched in biological processes related to neuron projection development, oligodendrocyte specification and differentiation leading to myelin components for central nervous system. The oligodendrocytes and astrocytes were considered key cellular contributors to the functional alterations.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that neural dysfunction during the recovery phase of anti-NMDAR encephalitis are closely linked to neurotransmitter systems and transcriptomic profiles. This multiscale integration bridges molecular mechanisms with neural dysfunction and may inform novel therapeutic strategies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107050"},"PeriodicalIF":5.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847919","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":"Spatiotemporal R-loop accumulation orchestrates microenvironmental remodeling after spinal cord injury","authors":"Zhipeng Jiang ,&nbsp;Youwei Guo ,&nbsp;Zihan Wang ,&nbsp;Jinhao Ouyang ,&nbsp;Haoxuan Huang ,&nbsp;Tianqian Shen ,&nbsp;Lei Wang ,&nbsp;Wen Yin ,&nbsp;Xingjun Jiang ,&nbsp;Caiping Ren","doi":"10.1016/j.nbd.2025.107055","DOIUrl":"10.1016/j.nbd.2025.107055","url":null,"abstract":"<div><div>Spinal cord injury (SCI) induces severe neurological dysfunction through direct mass cell damage and secondary inflammatory molecular cascades. These cascades—initiated by damage—recruit immune cells and amplify cytokine release, exacerbating neuronal death and tissue destruction. We initially report that R-loop accumulation (three-stranded RNA-DNA hybrids with displaced ssDNA) in neural injury contexts drives neurodegeneration via neuroinflammation. Utilizing annotated R-loop-associated genes (loci harboring RNA-DNA hybrids, resolvases, or functionally impacted by R-loops), we characterized fresh spinal cord tissues (50–100 mg) harvested from the cavity of injury (COI) (including gray/white matter) at 0, 1, 3, 7, and 14 days post-injury(dpi) in clip contusion models. Our research characterized dynamic post-injury expression patterns, including stage-specific upregulation of Cdk1, Top2a, Tp53, Tln1, and Flna. Spatial transcriptomics and immunofluorescence revealed significant R-loop accumulation in COI, correlating with tissue damage progression (loss of normal cellular architecture and expanding tissue cavitation quantified by HE/LFB staining). Applying cellular deconvolution—a computational approach inferring the proportional composition of distinct cell types by analyzing bulk-level molecular data—to SCI models, we observed dynamic microenvironment remodeling in COI. This process featured depletion of oligodendrocytes and neurons within post-injury, along with recruitment of diverse immune subsets including peripheral macrophages, bordering leukocytes, and activated microglia. Single-cell analysis and immunofluorescence staining ultimately identified Cdk1 as potentially involved in R-loop-associated microglial (Cd68⁺) inflammatory infiltration in COI at 7 dpi. These results provide the first evidence of R-loop's potential role in SCI progression, offering new insights for developing therapies aimed at preserving neurological function and promoting repair.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107055"},"PeriodicalIF":5.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822121","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":"Tauopathy strains differentially replicate in vitro in the presence of mutant tau monomer","authors":"Christine K. Brown ,&nbsp;Matthew P. Frost ,&nbsp;Sara A.M. Holec ,&nbsp;William W. Seeley ,&nbsp;Lea T. Grinberg ,&nbsp;Steven H. Olson ,&nbsp;Amanda L. Woerman","doi":"10.1016/j.nbd.2025.107052","DOIUrl":"10.1016/j.nbd.2025.107052","url":null,"abstract":"<div><div>Tauopathies are a group of neurodegenerative diseases caused by misfolding of the protein tau into a β-sheet rich conformation. By inducing misfolding of additional tau monomers, these pathogenic fibrils replicate and spread progressive disease throughout the brain. While frontotemporal lobar degenerative diseases (FTLDs) – including argyrophilic grain disease, corticobasal degeneration, globular glial tauopathy, and progressive supranuclear palsy – are caused by this same underlying molecular process, each disease is defined by a unique clinical and neuropathological presentation. This phenomenon is explained by the strain hypothesis, which proposes that the conformation tau misfolds into determines which disease a patient will develop. Indeed, robust structural and biological data indicate that tau misfolds into conformational arrangements specific to each disease. While these findings are highly impactful for understanding similarities and differences between tauopathies, they have yet to be harnessed to develop a definitive ante-mortem diagnostic. Working toward the goal of disease-specific diagnostics, we created a panel of tau bioreporter cell lines expressing a fragment of human tau fused to yellow fluorescent protein (YFP). Using point mutations designed to interfere with tau misfolding into specific conformations, we quantified YFP-positive puncta after incubating cells with tau fibrils from FTLD patient samples to establish a strain-specific profile for each tauopathy. Not only can we use this approach to differentiate between human tau strains, but we also show that the tau strain found in a commonly used mouse model exhibits properties that significantly differ from those seen in human patients.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107052"},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804461","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":"Gasdermin D is activated but does not drive neurodegeneration in SOD1G93A model of ALS: Implications for targeting pyroptosis","authors":"Georgia Gunner,&nbsp;Himanish Basu,&nbsp;Yueting Lu,&nbsp;Matthew Bergstresser,&nbsp;Liwei Sun,&nbsp;Dylan Neel,&nbsp;So Yoen Choi,&nbsp;Isaac M. Chiu","doi":"10.1016/j.nbd.2025.107048","DOIUrl":"10.1016/j.nbd.2025.107048","url":null,"abstract":"<div><div>Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) - the primary executioner of pyroptosis – remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1^G93A mouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1^G93A animals with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred C57Bl/6 J.SOD1^G93A mice onto a C57Bl/6NJ.GSDMD<em>-</em>deficient background. In comparing SOD1^G93A; <em>Gsdmd</em>+/+ and SOD1^G93A; <em>Gsdmd</em>−/− mice, we found that <em>Gsdmd</em> loss did not affect disease onset, weight loss, or grip strength decline in either male or female animals. Notably, GSDMD deficiency resulted in a modest but statistically significant increase in mortality in SOD1^G93A mice. Moreover, GSDMD absence had minimal impact on astrogliosis, microgliosis and motor neuron loss. These findings show that while GSDMD is activated in the ALS mouse model, its loss does not mitigate key ALS behavioral phenotypes, gliosis or motor neuron loss. This study provides insights into the potential therapeutic relevance of targeting pyroptosis and inflammatory pathways in ALS.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107048"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780094","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":"Expression of amyotrophic lateral sclerosis associated protein disulfide isomerase A3 D217N variant recapitulates early morphological alterations at the neuromuscular junction","authors":"Martin Sepulveda ,&nbsp;Francisca MartinezTraub ,&nbsp;Patricia Ojeda ,&nbsp;Jessica Mella ,&nbsp;Jorge Ojeda ,&nbsp;Cristina Pinto ,&nbsp;Rodrigo Diaz ,&nbsp;Pablo Rozas ,&nbsp;Claudia Sepulveda ,&nbsp;Bredford Kerr ,&nbsp;Vania Morales ,&nbsp;Mirva Saaranen ,&nbsp;Lloyd Ruddock ,&nbsp;Danilo B. Medinas ,&nbsp;Juan Pablo Henriquez ,&nbsp;Claudio Hetz","doi":"10.1016/j.nbd.2025.107045","DOIUrl":"10.1016/j.nbd.2025.107045","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by neuromuscular connectivity decline followed by motoneuron loss. Altered proteostasis is suggested as a transversal pathogenic mechanism, notably involving dysfunction at the level of the endoplasmic reticulum (ER). Protein disulfide isomerases (PDIs) are key enzymes that catalyze protein folding and disulfide bond formation in the ER. Importantly, PDIs function is disrupted in ALS. We previously identified mutations in the gene encoding PDIA3 (also known as Grp58 or ERp57) as risk factors for ALS, which were associated with altered neuromuscular junction (NMJ) organization when expressed in zebrafish, a phenotype recapitulated in PDIA3-null mice. Here, we generated a transgenic mouse line overexpressing the ALS-linked PDIA3 variant D217N and performed a comprehensive characterization of ALS-like features. The transgenic line exhibited moderate overexpression of mutant PDIA3^D217N, which led to morphological alterations at the NMJ resembling those observed in ALS models and patients, along with abnormal distribution of oxidative and glycolytic muscle fibers. However, mutant PDIA3^D217N expression did not result in motor impairment, coordination deficits, or motoneuron loss. At the molecular level, we observed reduced expression of SV2 in the spinal cord, an important synaptic protein involved in NMJ function. Our findings further support the involvement of PDIA3 dysfunction as a risk factor in the emergence of early features of ALS.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107045"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775869","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":"Transgenic expression of the human Glucose Transporter1 (GLUT1) gene locus reduces disease burden in Glut1 deficiency syndrome model mice","authors":"Maoxue Tang ,&nbsp;Sasa Teng ,&nbsp;Ashley Y. Kim ,&nbsp;Yueqing Peng ,&nbsp;Umrao R. Monani","doi":"10.1016/j.nbd.2025.107047","DOIUrl":"10.1016/j.nbd.2025.107047","url":null,"abstract":"<div><div>Proper brain function relies on an adequate supply of energy – mainly glucose – to power neuronal activity. Delivery of this nutrient to the neuropil is mediated by the Glucose Transporter1 (GLUT1) protein. Perturbing glucose supply to the brain is profoundly damaging and exemplified by the neurodevelopmental disorder, GLUT1 deficiency syndrome (GLUT1DS). Resulting from haploinsufficiency of the <em>SLC2A1 (GLUT1)</em> gene, GLUT1DS is characterized by intractable infantile-onset seizures and a disabling movement disorder. Ketogenic diets, which supply the brain with an alternate energy source, ketone bodies, are currently the preferred therapeutic option for Glut1DS patients but do not address the underlying cause – low brain glucose – of the disease. One intuitively appealing therapeutic strategy that does, involves restoring GLUT1 levels to the patient brain. Here, we demonstrate that transgenic expression of the human <em>GLUT1</em> genomic locus in a mouse model of GLUT1DS raises brain GLUT1 levels and reduces disease burden. Augmenting GLUT1 levels in mutants correspondingly raised cerebrospinal fluid (CSF) glucose levels, improved motor performance and reduced the frequency of seizures characteristically observed in GLUT1DS. Interestingly, the increased GLUT1 in mutants harboring the human <em>GLUT1</em> locus was at least partly the result of an increase in murine <em>Slc2a1 (Glut1)</em> activity, most likely the effect of a long non-coding RNA (lncRNA) embedded in the human transgene. Collectively, our work has not only shown that repleting human GLUT1 mitigates GLUT1DS but also has yielded transgenic mice that constitute a useful tool to test and optimize clinically promising agents designed to stimulate this gene for therapeutic purposes.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107047"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771346","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":"Expression of concern: \"Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury\" [NEUROBIOL DIS, Volume 51 (2013) Pages 133-143].","authors":"","doi":"10.1016/j.nbd.2025.106949","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.106949","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"212 ","pages":"106949"},"PeriodicalIF":5.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302572","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}