A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects.

Gliomas, ranging from low-grade pilocytic astrocytomas to highly malignant glioblastomas, are primary brain tumors that originate from neural or glial stem cells. Classified by the WHO into grades 1 to 4, these tumors exhibit varying prognoses, with oligodendrogliomas and astrocytomas having better and intermediate outcomes, respectively, while glioblastomas are associated with a poor prognosis. Despite advancements in molecular and genetic research that have improved diagnosis and the development of targeted therapies, treating high-grade gliomas remains a significant challenge due to their diffuse nature. In this context, lectins, carbohydrate-binding proteins, have shown promise as diagnostic and therapeutic agents for cancer, including gliomas. Plant lectins, particularly those from legumes, exhibit significant antiproliferative effects on glioma cells. These effects include decreased cell viability and migration, alongside the induction of autophagy and apoptosis, suggesting their potential as therapeutic agents. Although the mechanisms underlying these effects are not yet fully understood, molecular targets and pathways involved in the antiglioma activity of lectins have been identified. Key targets include matrix metalloproteinases (MMPs), epidermal growth factor receptor (EGFR), CD98 (xc^- system), AMPA receptor, and CD73. This review focuses on the antiglioma potential of legume lectins, their applications, and the main molecular targets based on their functions, structures, and associated molecular mechanisms.

Lectins, proteins that reversibly bind specific glycan motifs, offer dual utility as molecular probes or inhibitors of virus-host interactions. This review explores the molecular interactions between lectins and viral envelope glycoproteins, emphasizing their applications as antiviral agents and diagnostic tools. Enveloped viruses, such as HIV, Influenza, Herpesviruses, and Coronaviruses, exhibit dense glycosylation on their surface proteins, forming a glycan shield rich in high-mannose and complex glycans crucial for viral processes and immune evasion. Lectins exploit these glycan shields by selectively targeting conserved glycosylation sites on key viral proteins like gp120 (HIV), hemagglutinin (Influenza), spike (SARS-CoV-2), and glycoprotein D (HSV), thereby interfering with viral entry. Potent inhibitory activity across diverse virus families has been demonstrated for natural lectins such as griffithsin (GRFT), cyanovirin (CV-N), and banana lectin (BanLec), with novel fungal and algal lectins continually expanding the list. Concurrently, lectin-based biosensors utilizing electrochemical, plasmonic, and microfluidic platforms, often enhanced by nanomaterials or aptamers, enable sensitive and specific detection of glycosylated viral targets. Despite challenges including potential immunogenicity and production scalability, ongoing bioengineering efforts aim to refine lectin specificity, reduce toxicity, and enhance overall functionality. These collective advances showcase the role of lectins as versatile molecular tools for the detection, inhibition, and mechanistic study of viral pathogens.

Studies have revealed the dependence of glioma cells on iron, making them sensitive to ferroptosis. Ferroptosis can be triggered by inhibition of the xc- system, resulting in redox imbalance and membrane lipid peroxidation. The xc- system is composed of two coupled proteins, xCT and CD98hc. The control of transporters, such as xCT, by the CD98hc glycoprotein suggests that molecules targeting glycans may have an impact on the treatment of glioma. This study evaluated the effect of the Canavalia brasiliensis (ConBr) lectin on C6 glioma cells and compared it with erastin, an xc- system inhibitor. Both induced dose-dependent cell death, accompanied by an increase in the production of reactive oxygen species and a decrease in reduced glutathione. However, co-treatment did not show an additive effect. The analysis was updated by molecular dynamics assessments of the xc- system interacting with ConBr or erastin. The interaction of erastin with the xc- system affects its interaction with ConBr, reducing the antagonistic effect when both are in the protein complex. The data show that ConBr is effective in inducing cell death in glioma cells and regulates the xc system through interaction with CD98hc glycans, showing that lectins have the potential to promote ferroptosis in glioma cells.

Autism spectrum disorder is increasingly linked to altered microglial biology. However, current research models are limited by outdated descriptions of microglial “activation”. Here, we propose that microglial involvement in ASD is best understood as a problem of state mismatch, in which temporally programmed and regionally specialized microglial states fail to align with local developmental demands. We synthesize evidence across genetic models, human transcriptomics, and experimental systems to examine three axes of misalignment: developmental timing, circuit specificity, and functional phenotype. These mismatches produce divergent outcomes, including both excessive and insufficient synaptic pruning, and reflect a decoupling between microglial activation markers and effector capacity. We further evaluate molecular recognition systems governing microglia–synapse interactions, with emphasis on complement signaling and glycan-mediated pathways such as sialic acid–Siglec signaling and polysialylation. While glycosylation is not a universal driver of ASD pathology, it represents a plausible regulatory layer controlling synapse visibility and microglial engagement. This framework reconciles conflicting findings in the literature and positions microglia as dynamic developmental effectors whose misaligned state trajectories contribute to circuit-level dysfunction in ASD.

Background/Objective: New therapeutic targets are urgently needed for glioblastoma, the most aggressive primary brain tumor in adults. Monepantel (MPL), a repurposed anthelmintic, is thought to act in cancer cells through ATF4-mediated endoplasmic reticulum (ER) stress that inhibits mTORC1, but this axis had not been examined in glioma. The present study aimed to evaluate the effects of monepantel (MPL) in rat C6 glioma and human U87-MG glioblastoma cells, focusing on the ER stress/mTOR/autophagy signaling network. Methods: Cells were treated with MPL, and cell viability was measured by MTT assay. The signaling pathways were analyzed by Western blotting, and autophagy by acridine orange staining and LC3-II detection. Cell migration was assessed using a scratch wound-healing assay and tumorspheres. Results: MPL increased the ER chaperone BiP/GRP78 and induced autophagy, as shown by concentration-dependent accumulation of acidic vesicular organelles and LC3-II. In parallel, MPL reduced phosphorylation of the mTORC1 substrate p70S6K, without affecting Akt, localizing its action at or below mTORC1, suggesting an ER-stress-to-autophagy route. MPL additionally produced a decrease in ERK2 phosphorylation, while p38^MAPK was unchanged. These molecular changes were accompanied by reduction in C6 viability and by impaired C6 migration and reduced U87-MG tumorsphere migratory area. Conclusions: Together, these data suggest that MPL engages an ER-stress/mTORC1 axis associated with autophagy and ERK2 inhibition in glioma. These findings indicate the potential of MPL as an antiglioma agent. However, further studies using additional cell lines, together with preclinical testing, are needed to better characterize its effects and determine its potential for future clinical application.