Search Results (228)

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection. Full article

Terrestrial environments function as major sinks and dynamic sources of microplastics. Land use strongly influences inputs, accumulation, and transport pathways of these contaminants in the environment. Despite the extensive literature, few reviews have compared contamination levels and the potential impacting factors across land uses. To fill this gap, this review synthesizes current knowledge on the origins, occurrence, pathways, and ecological effects of microplastics across diverse land uses. The review revealed multiple interconnected pathways that drive microplastic contamination in terrestrial systems. Abundances are consistently higher in intensively managed croplands, urban areas and industrial vicinities. However, their detection in remote environments underscores the critical role of diffuse inputs and long-range atmospheric transport. Vertically, microplastics are enriched in topsoils, and their concentrations declines with depth. Horizontally, concentration declines with increasing distance from major hotspots like agricultural fields, industrial facilities, and road networks. Ecologically, microplastics alter soil physical properties, modify chemical conditions, and shift microbial community composition and enzyme activities. Furthermore, they stress soil fauna and plants through ingestion, toxicity, and physical blockage, with impacts contingent on polymer type, particle morphology, and concentration. Collectively, this review reveals consistent spatial patterns and widespread adverse ecological impacts, highlighting the clear need for integrated management strategies to mitigate terrestrial microplastic pollution. Full article

ZmSIG2A is a nuclear-encoded plastid sigma factor 2A in maize (Zea mays L.) that is essential for plastid gene transcription and chloroplast biogenesis. As a key regulator of chloroplast development and function, ZmSIG2A may also contribute to the coordination of plant growth and environmental adaptation; however, its roles in root development and stress responses remain largely unclear. We compared two ZmSIG2A mutants, eal1-1 (hypomorphic) and ems110 (nonsense). eal1-1 had increased root number and longer roots, while ems110 had normal root number but shorter roots and failed to mature. The zmsig2a^Val480del transcript was upregulated in eal1-1, and the root-promoting effect of OsSIG2A in rice suggests a conserved role in monocot root growth. DAP-seq indicated that zmsig2a^Val480del targets are involved in metabolism, transport, signaling, and antioxidants, with Chr4 peak clustering near multiple LRR-RLKs, suggesting a ZmSIG2A–LRR-RLK module in root development and stress integration. Physiologically, eal1-1 showed increased antioxidant enzyme activities and reduced MDA, indicating enhanced ROS scavenging, while ems110 exhibited decreased enzyme activities and elevated MDA, indicating compromised ROS detoxification. Upstream, Y1H and dual-luciferase assays demonstrated that the Mediator subunit ZmMed31 positively regulates transcription from the ZmSIG2A promoter. Given Mediator’s role in bridging transcription factors and the core transcriptional machinery, ZmMed31 likely links hormone-responsive transcription factors to the ZmSIG2A regulatory network. Collectively, we propose a stress-responsive ZmMed31–ZmSIG2A–LRR-RLK module that underpins maize root development and drought adaptation, offering mechanistic insight and potential targets for stress-resilient breeding. Full article

Cell-free protein synthesis has become a powerful tool for producing functional proteins, circumventing many limitations of live-cell systems. Platforms based on wheat germ extract are favored for their high efficiency in translating and folding complex eukaryotic proteins. To overcome the energy limitation common in such systems, we engineered an Escherichia coli strain to function as a self-renewing ATP source. This strain co-expresses a three-enzyme cascade—adenosine kinase, adenylate kinase, and acetate kinase—that efficiently converts adenosine and acetyl phosphate into ATP. Using the lysate from this biocatalyst to energize an optimized wheat germ extract, we established a high-performance cell-free synthesis platform. This integrated system supported the robust production of multiple recombinant proteins. As a key demonstration, we synthesized human vascular endothelial growth factor 165, which exhibited full biological activity. The cell-free-produced VEGF₁₆₅ significantly stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). It also potently induced angiogenic responses, including the formation of extensive, interconnected capillary-like networks by HUVECs in vitro and accelerated cell migration in scratch-wound assays. Our work establishes a scalable and efficient platform for on-demand production of bioactive eukaryotic proteins, highlighting its considerable potential for advancing regenerative medicine and related therapeutic applications. Full article

The SARS-CoV-2 papain-like protease (PL^pro) is an essential viral enzyme that promotes viral polyprotein processing while simultaneously suppressing the host innate immune response, which makes it a primary target for developing antiviral drugs. The present study employs a comprehensive approach integrating untargeted metabolomic profiling, in silico molecular docking and dynamics simulations, Molecular Mechanics Generalized Born Surface Area (MM-GBSA) energetic assessments, and biochemical enzyme assays. This integrated method aims to discover natural PL^pro inhibitors from two ethnomedicinal plants, Lippia javanica and Acorus calamus, which have long been utilized in African traditional medicine to treat respiratory diseases. Comprehensive metabolite profiling using untargeted Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) and Global Natural Products Social (GNPS) molecular networking revealed flavonoid glucuronides and phenylpropanoid derivatives as the major constituents in both plant species. In situ histochemical staining further offered spatial validation of phenolic- and lignin-associated tissues, supporting the phenolic-dominated molecular families detected by GNPS molecular networking. In silico evaluation of six selected compounds demonstrated spontaneous and thermodynamically favorable binding to PL^pro, with ΔG_bind values ranging from −5.63 to −6.43 kcal/mol. Catechin-7-glucoside emerged as the lead compound, establishing multiple hydrogen bond networks with Asp164, Gln269, Tyr264, and Asn267, supplemented by hydrophobic engagement with Pro247 and Pro248, and π-π stacking with the blocking loop 2 (BL2 loop). Molecular dynamics simulations confirmed the stability of the protein–ligand complexes. Biochemical enzyme assays confirmed concentration-dependent inhibition of PL^pro proteolytic and deubiquitinating activity by both crude plant extracts and isolated bioactive compounds. However, S-adenosyl-methionine showed comparatively high PL^pro proteolytic activity (IC₅₀ 5.872 µM) compared to catechin-7-glucoside, with an IC₅₀ of 7.493 µM, exhibiting efficacy similar to the reference inhibitor GRL0617. Both the extracts of L. javanica and A. calamus have shown significant inhibitory activity while maintaining cell viability in Human embryonic kidney 293T cell (HEK293T) culture models, indicating a favorable safety profile of the tested concentrations. Based on these results, catechin-based polyphenols and phenylpropanoid derivatives appear as promising lead compounds for the development of PL^pro inhibitors. To progress toward therapeutic use, further work is necessary in pharmacokinetics, structural optimization, and antiviral validation in cell models. Full article

Coronaviruses pose a global pandemic threat, making development of a pan-coronavirus inhibitor crucial for preparedness and containment in the event of a new coronavirus outbreak. The 3C-like protease (3CL^pro) is a key target for antiviral development, as it is essential for viral replication and conserved across human coronaviruses. We previously developed an assay to monitor SARS-CoV-2 3CL^pro activity in cells. This assay uses a single vector that coexpresses the 3CL^pro enzyme and the reporter, which consists of two luciferase fragments linked by a 3CL^pro cleavage site. Cleavage of this site by 3CL^pro decreases luciferase activity, whereas inhibition of 3CL^pro increases the luciferase activity. Here, we adapted this assay to examine 3CL^pro activity from six other human coronaviruses: SARS-CoV, MERS-CoV, HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1. We further determined the effects of different cleavage sites to improve the signal-to-background ratio. The Nsp4-Nsp5 site and super-active substrate (SAS) resulted in the largest dynamic range for most coronaviruses in our assay. Using the broad-spectrum 3CL^pro inhibitor GC376, we observed increased reporter activity, indicating the assay’s efficacy for identifying inhibitors across multiple coronaviruses. The adaptation and improvement of the assay can facilitate the development of inhibitors against 3CL^pro from multiple or novel coronaviruses. Full article

Plant-parasitic nematodes (PPNs) cause big crop losses globally. Safe/reliable methods for their durable management strategies can harness various beneficial relationships among the plant immune system and related microbiomes. Molecular mechanisms basic to these relations reveal wide arrays of significant roles for plant-healthy growth. This review focuses on such relations of microbiomes to prime and immunize plants against PPNs. It also highlights molecular issues facing PPN-resistant varieties with possible solutions such as genetic breeding/engineering, grafting, PPN-antagonistic root exudates, and novel resistant cultivars. These issues call for optimal uses of various widespread groups of microbiomes. Related plant signaling hormones and transcription factors that regulate gene expression and modulate nematode-responsive genes to ease positive/negative adaptation are presented. Exploring PPN-resistance genes, their activation mechanisms, and signaling networks offers a holistic grasp of plant defense related to biotic/abiotic factors. Such factors relevant to systemic acquired resistance (SAR) via plant–microbe interactions to manage PPNs are stressed. The microbiomes can be added as inoculants and/or steering the indigenous rhizosphere ones. Consequently, SAR is mediated by the accumulation of salicylic acid and the subsequent expression of pathogenesis-related genes. To activate SAR, adequate priming and induction of plant defense against PPNs would rely on closely linked factors. They mainly include the engaged microbiome species/strains, plant genotypes, existing fauna/flora, compatibility with other involved biologicals, and methods/rates of the inoculants. To operationalize improved plant resistance and the microbiome’s usage, novel actionable insights for research and field applications are necessary. Synthesis of adequate screening techniques in plant breeding would better use multiple parameters (molecular and classical ones)-based ratings for PPN-host suitability designation. Sound statistical analyses and interpretation approaches can better identify genotypes with high-level, stable resistance to PPNs than the commonly used ones. Linking molecular mechanisms to consistent field relevance can be progressed via dissemination of many advanced techniques. The CRISPR/Cas9 system has been effective in knocking out both the OsHPP04 gene in rice to confer resistance against Meloidogyne graminicola and the GhiMLO3 gene in cotton to minimize the Rotylenchulus reniformis reproduction. Its genetic modifications in crops synthesized “transgene-free” PPN-resistant plants without decreased growth/yield. Characterizing microbiome species/strains needed to prime and immunize plants requires better molecular tools for fine-scale taxonomic resolution than the common ones used. The former can distinguish closely related ones that exhibit divergent phenotypes for key attributes like stability and production of enzymes and secondary metabolites. As PPN-control strategies via tritrophic interactions are more sensitive to the relevant settings than chemical nematicides, it is suggested herein to test these settings on a case-by-case basis to avoid erratic/contradictory results. Moreover, expanding the use of automated systems to expedite detection/count processes of PPN and related microbes with objectivity/accuracy is discussed. When PPNs and their related microbial distribution patterns were modeled, more aspects of their field distributions were discovered in order to optimize their integrated management. Hence, the feasibility of site-specific microbiome application in PPN–hotspot infections can be evaluated. The main technical challenges and controversies in the field are also addressed herein. Their conceptual revision based on harnessing novel techniques/tools is direly needed for future clear trends. This review also engages raising growers’ awareness to leverage such strategies for enhancing plant resistance and advancing the microbiome role. Microbiomes enjoy wide spectrum efficacy, low fitness cost, and inheritance to next generations in durable agriculture. Full article

The endoplasmic reticulum (ER) responds to stimuli that disrupts its homeostasis by activating a signalling network known as unfolded protein response (UPR), that restores cellular balance and determines cell fate through three key sensors: inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6 (ATF6), and protein kinase RNA-like ER kinase (PERK). Emerging evidence suggests that UPR regulates the expression of numerous long non-coding RNAs (lncRNAs), which play critical roles in maintaining ER homeostasis. Here we show that expression of lncRNA H19 is downregulated in response to ER stress in (MCF7, T47D and 293T) cells. Using genetic and pharmacological approaches, we demonstrate that H19 downregulation is primarily mediated by the PERK arm of the UPR. Specifically, knockdown or chemical inhibition of PERK compromised the ER stress-mediated H19 repression, while PERK activation significantly reduced H19 expression. H19 overexpression promotes the optimal activation of ATF6 and PERK pathways, while it attenuates the signalling by IRE1-XBP1 axis of the UPR. Furthermore, in triple-negative breast cancer (TNBC) cells MDA-MB-231, ectopic H19 provided resistance to ER stress-induced apoptosis. Bioinformatic analyses across multiple breast cancer cohorts revealed that high H19 expression was associated with poor prognosis, particularly in basal-like subtypes. Collectively, our findings show that H19 is downregulated during UPR in a PERK-dependent manner, where H19 in turn modulates UPR signalling and cell fate during conditions of ER stress. Full article

Background/Objectives: Choline plays an important role in maintaining normal cellular function and overall physiology. Endogenous choline availability depends on the synthesis of phosphatidylcholine via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway. Expression of PEMT is influenced by estrogen, as its promoter contains multiple estrogen-responsive elements that enhance enzyme activity. How a low estrogenic condition like menopause influences choline’s effect on the brain is not yet fully understood. Methods: In this pilot study, 20 women participated in two study days, with 1650 mg of oral choline bitartrate or a matching placebo administered three hours before a functional and structural magnetic resonance imaging (MRI) scan. Blood oxygen level dependent (BOLD) functional MRI scans were collected on each study day while subjects performed an N-back working memory task. Results: In this pilot study, no differences in working memory performance were observed, but decreased activation was found for the choline compared to the placebo during the 2-back compared to 0-back conditions in regions of the right temporal lobe (p < 0.001 voxel-level threshold, and p-FDR < 0.05 cluster-size threshold). When we seeded the right planum temporale to examine its functional connectivity with the rest of the brain, we found that choline modulated a large portion of the working memory network during the difficult memory load condition. Conclusions: These results in this pilot study illustrate the effect of choline on working memory-related brain activation and functional connectivity in postmenopausal women. We propose that choline may increase brain functional efficiency in low estrogenic conditions like menopause, but further studies are needed. Full article

In this study, a silver-based metal–organic framework (Ag-MOF) nanozyme was synthesized for the synergistic eradication of drug-resistant Salmonella enteritidis in food matrices. Ag-MOF exhibits multiple enzyme-like activities, namely oxidase (OXD)-, peroxidase (POD)-, and superoxide dismutase (SOD)-like activities. It demonstrated excellent antibacterial and antibiofilm activities against erythromycin- and chloramphenicol-resistant S. enteritidis strains (N29 and P23). Specifically, treatment with 20 mg mL⁻¹ Ag-MOF resulted in nearly complete eradication of S. enteritidis in in vitro suspension assays, including 1 × 10⁷ CFU mL⁻¹ N29 strain and 6 × 10⁶ CFU mL⁻¹ P23 strain. Moreover, treatment with 1 mg mL⁻¹ Ag-MOF led to 80~90% biofilm inhibition of S. enteritidis. Mechanistic investigations revealed that Ag-MOF effectively interacted with amino-rich structures on the bacterial surface (such as membrane proteins and peptidoglycan components), generated abundant reactive oxygen species (ROS), released Ag⁺ ions, and depleted intracellular glutathione, which collectively disrupted cell membrane integrity and induced severe leakage of intracellular proteins and nucleic acids. Importantly, Ag-MOF maintained high antibacterial efficacy in complex simulated food matrices (pork, milk, and egg shell). Overall, this study offers key insights into enzyme-mimicking antibacterial materials and a promising strategy to combat multidrug resistant foodborne pathogens. Full article

Bacillus licheniformis Mb1, a thermophilic strain isolated from the Yungas rainforest in northwestern Argentina, was analyzed through genomic and experimental approaches to explore its biotechnological potential. Phylogenomic analysis confirmed its close relationship with B. licheniformis reference strains. The genome revealed multiple genes associated with hydrolytic, oxidative, carbohydrate-active, and polyester-degrading activities, indicating a wide enzymatic capacity. Experimental assays demonstrated strong extracellular hydrolytic activities and efficient degradation of bis(2-hydroxyethyl) terephthalate (BHET), a key polyethylene terephthalate (PET) intermediate. In liquid cultures with 3 mg/mL BHET, B. licheniformis Mb1 achieved 99.9% depletion within four days, with transient BHET dimer accumulation and progressive terephthalic acid (TPA) production, reaching 1.17 mg/mL after 15 days. Mono (2-hydroxyethyl) terephthalate (MHET) and vanillic acid were not detected. Complete BHET and dimer degradation suggests the presence of versatile hydrolases acting on short-chain polyester intermediates. Sequence and molecular docking analyses identified a BHETase-like carboxylesterase as the main enzyme candidate, featuring a truncated lidC region that generates a more open catalytic cleft. This structural trait, not previously reported in bacterial BHETases, enables the accommodation of bulkier substrates such as BHET dimer. These findings highlight B. licheniformis Mb1 as a promising biocatalyst for polyester depolymerization and a valuable microbial resource for future enzyme discovery and plastic bioremediation strategies. Full article

Candidatus Liberibacter spp. can infect most citrus plants and rely entirely on phloem sieve tube cells of the host plant for survival. Candidatus Liberibacter primarily contains Ca. L. asiaticus (CLas), Ca. L. africanus (CLaf), and Ca. L. americanus (CLam). Among these, CLas is the most harmful and widely distributed and is the primary pathogen of the devastating citrus disease Huanglongbing (HLB). Effectors are among the core weapons secreted by pathogens into plant cells to attack the plant immune system. In this study, we focused on CLas-specific effectors and those that are highly expressed during the infection stage to identify essential virulence effectors. Using secretion signal peptide prediction analysis, 40 candidate effectors with potential secretory capabilities were identified. Transient expression of these candidate effectors in Nicotiana benthamiana revealed their impact on pattern-triggered immunity, including INF-induced cell death and microbial pattern-induced reactive oxygen species (ROS) bursts, and the resistance of N. benthamiana to the bacterial pathogen Pst DC3000. 10 candidate effectors capable of suppressing plant immunity were identified. The stable expression of these candidate effectors in Arabidopsis showed that several candidate effectors enhanced plant susceptibility to Pst DC3000 and inhibited flg22-induced ROS production and MAPK activation. Among the three candidate effectors that significantly suppressed ROS burst, one effector, E3 (CLIBASIA_03085), interacts with the plant NADPH oxidase RbohD, a key enzyme responsible for ROS production. This suggests that E3 likely inhibits ROS accumulation by directly targeting RbohD. Here, we identified multiple candidate effectors capable of suppressing microbial pattern-triggered immunity that may be essential virulence factors for CLas infection, enhancing our understanding of CLas pathogenesis. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

The aim of this study was to acquire endospore-former(s) for aquatic animal feed based on the probiotic potential in vitro, including the anti-pathogen spectrum, gastrointestinal fluid tolerance, antioxidant activity, enzyme-producing ability, and basic safety assessment. The strain Bacillus velezensis FJAT-57093 was found to exhibit the strongest antibacterial ability against Aeromonas hydrophila in the agar well diffusion inhibition assays from 111 Bacillus-like strains. Moreover, the results showed that the compounds of the strain FJAT-57093 enriched by acid precipitation might be the main antibacterial metabolites. The strain FJAT-57093 also exhibited antibacterial effects against the aquatic pathogens Photobacterium damselae, Edwardsiella tarda, Vibrio parahaemolyticus, and Vibrio vulnificus. The safety assessment revealed that the strain FJAT-57093 was non-hemolytic and susceptible to ten antibiotics. The putative virulence and antibiotic resistance genes predicted were predominantly intrinsic to the FJAT-57093 genome. Furthermore, the strain FJAT-57093 demonstrated a tolerance of acid and bile salt under the simulated gastrointestinal tract conditions, extracellular enzyme-producing abilities, as well as an auto-aggregation rate of 45.88% at 24 h and co-aggregation rates with the aforementioned five aquatic pathogens, ranging from 14.87% to 58.55%. Additionally, its extracellular metabolites displayed strong antioxidant activities, with ABTS⁺ and DPPH radical scavenging rates of up to 99.82% and 42.74%, respectively. In summary, the strain B. velezensis FJAT-57093 was found to possess strong antibacterial activities against multiple aquatic pathogens and desirable in vitro probiotic properties. Full article

Background: The insulin-like growth factor 2 receptor (IGF-2R), also known as the cation-independent mannose 6-phosphate receptor (CI-M6PR), is emerging as a critical receptor for brain function and disease. IGF-2R, in fact, plays a key role in long-term memory, and its activation by several ligands shows beneficial effects in multiple neurodevelopmental and neurodegenerative disease models. Thus, its targeting is very promising for neuropsychiatric therapeutic interventions. IGF-2R’s main known functions are transport of lysosomal enzymes and regulation of developmental tissue growth, but in the brain, it also controls learning-dependent protein synthesis underlying long-term memory. However, little is known about this receptor in brain cells, including its cell-type-specific and subcellular expression. Methods: We conducted a comprehensive investigation to comparatively assess IGF-2R protein levels in different brain cell types across various brain regions in adult male C57BL/6J mice using dual and multiplex immunofluorescent staining with cell-type-specific markers. The IGF-2R protein distribution was also compared with Igf2r mRNA expression in publicly available single-cell RNA sequencing databases. Results: A ranking of IGF-2R levels in the soma of various cell types in the hippocampus and cortical regions revealed that the highest enrichment is, by far, in excitatory and inhibitory neurons, followed by vascular mural cells and subpopulations of oligodendrocyte lineage cells, with low to undetectable levels in astrocytes, microglia, vascular endothelial cells, and perivascular fibroblasts. High levels of IGF-2R were also found in ependymal cells, choroid plexus epithelial cells, and a subpopulation of meningeal fibroblast-like cells. IGF-2R was found in dendritic and putative axonal compartments throughout the brain, with particularly high levels in the stratum lucidum. The receptor’s protein distribution aligned with that of the mRNA in mouse brain databases. Conclusions: These results suggest that IGF-2R-mediated functions in the brain vary across different cell types and subcellular compartments, with the most active roles in specific subpopulations of neurons, mural cells, ependymal cells, meningeal cells, and cells of the oligodendrocyte lineage. This study advances our understanding of IGF-2R’s distribution in the brain, which is essential for formulating new hypotheses about its functions and therapeutic targeting. Full article