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 However, current research models are limited by outdated descriptions of microglial “activation”.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.

Previous study demonstrated that Hypnea cervicornis lectin (HCA) reduces inflammation and nociception via interaction with the lectin carbohydrate-binding site, modulating gene expression of the interleukins IL-1β, TNF-α and of iNOS. This study evaluated the effect of HCA in the rat model of arthritis induced by zymosan in the tibiotarsal joint and the involvement of macrophage-derived mediators. In vitro, macrophages were stimulated with zymosan before being incubated with HCA and the supernatant was injected into the joint. In vivo, HCA was administered by intravenous route after intra-articular injection of zymosan, fMLP, or macrophages supernatant. Hypernociception, edema and leukocyte influx were evaluated in the joints, and inflammatory mediators in the macrophage supernatant or periarticular tissue. In vitro, HCA (100 µg/ml) reduced NO2− and IL-1β in the supernatant of macrophages. In vivo, HCA (3 mg/kg) reduced articular hypernociception, edema and leukocyte influx elicited by zymosan, fMLP or by the supernatant of zymosan activated macrophages, as well as the zymosan-induced rolling and adhesion, and gene expression of iNOS and IL-1. HCA attenuated edema and leukocyte influx in the periarticular tissue, revealing preserved chondrocytes in the cartilage. In conclusion, HCA exerts anti-inflammatory effect in the arthritis induced by zymosan in rat tibio-tarsal joints, involving NO and IL-1 released by resident macrophages.

Lectins are proteins or glycoproteins capable of binding specifically and reversibly to carbohydrates, a property that, in itself, gives them great functional versatility in organisms from all kingdoms of nature. A subclass of these proteins, called chimerolectins, is composed of proteins that have at least one lectin domain associated with another functional domain, such as enzymatic domains or modules involved in molecular signaling processes. The emergence of chimerolectins throughout evolution significantly expanded the functional repertoire of lectins, allowing their action to go beyond the interaction with carbohydrates and glycoconjugates. These proteins are involved in the regulation of the immune system in humans and animals, in the defense of plants against pathogens and predators, as well as in the mediation of responses to biotic and abiotic stresses. In addition, they can act as potent lethal toxins or as factors in the infection of several pathogens and are often associated with the manifestation of symptoms of diseases, which makes them therapeutic targets of great interest. Deepening the structural knowledge of these proteins has been essential for understanding their mechanisms of action, in addition to providing solid bases for biotechnological applications and for the rational development of artificial lectins with specific functions. This approach has enabled the creation of chimerolectins with potent antiviral activity, as well as the development of new therapeutic strategies aimed at inducing death in cells of different tumor lineages.

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.

Diocleinae lectins are well known for their prevalent affinity for glycomannosides. However, a rare subset displays specificity towards galactosides. This study describes the characterization of DrfL II, a novel lectin from Dioclea relexa seeds with specificity for N,N '-diacetyl-lactosamine (LacdiNAc). Isolated by lactose-affinity chromatography, DrfL II exists as a homotetramer formed by associations of a 29 kDa chainis a tetrameric lectin composed of identical 29 kDa subunits and strongly agglutinates rabbit erythrocytes, an activity inhibited by alpha-lactose. DrfL II binds preferentially to LacdiNAc (GalNAc beta 1-4GlcNAc) over N-acetyl-lactosamine (LacNAc, Gal beta 1-4GlcNAc), functioning optimally between pH 6-8 and retaining stability up to 60 degrees C. Partial protein sequencing revealed homology with other legume lectins. Beyond its distinct carbohydrate specificity, DrfL II induced significant inflammatory and hypernociceptive responses in mice, as shown by paw edema and von Frey assays, while remaining non-toxic to Artemia nauplii. This finding expand our understanding of the galactosidespecific lectins within the Diocleinae subtribe, suggesting potential roles in physiological processes yet to be fully elucidated and potential biological application within the inflammation field.

The genus Centrolobium comprises species of Neotropical trees with seeds that possess medicinal and bioactive applications. Lectins from this genus exhibit anti-inflammatory and immunomodulatory effects, influencing the activation of the immune system. This study focuses on characterizing the structure and carbohydrate-binding properties of the lectin from Centrolobium microchaete (CML) and evaluating its potential against gliomas. The structure of the lectin in complex with methyl-mannose-α1,3-mannose (MDM) was resolved using X-ray crystallography at 1.3 Å resolution, with its interactions further analyzed through molecular dynamics simulations. Structurally, CML adopts a β-sandwich motif and assembles into canonical dimers. In vitro assays revealed that CML reduced the viability of C6 glioma cells, although only at high concentrations, without impacting cell migration or morphology. CML activated autophagic processes, albeit with lower efficacy compared with other mannose-specific lectins. The limited antiglioma activity of CML may be linked to its inability to form tetramers and unusual specificity toward asymmetric glycans, both crucial features for interactions with cellular glycans and the activation of signaling pathways. This study represents the first investigation of the antiglioma potential of a mannose-specific lectin from the Dalbergieae tribe, highlighting both its structural characteristics and functional limitations.

Lectins play crucial roles in many biological processes and serve as tools in fields ranging from agriculture to biomedicine. While classical methods for lectin discovery and characterization were foundational for the field, they often lack sensitivity and throughput, limiting the detection of less abundant or weakly binding lectins, such as the stress-inducible or monovalent lectins. This review focuses on recent advancements in plant lectin research, particularly novel technologies that complement traditional approaches. Techniques such as glycan microarrays allow rapid assessment of lectin specificity across a diverse range of glycans by evaluating interactions with immobilized glycans on solid surfaces. Phage display libraries enable the identification of carbohydrate-mimetic peptides and the development of ligands for lectins by presenting diverse peptide libraries on bacteriophages. Genomic and transcriptomic analyses facilitate the exploration of the lectome in various plant species by scanning entire datasets to identify genes that contain lectin motifs—specific conserved amino acid sequences involved in carbohydrate recognition—and lectin domains, the larger structural regions that facilitate and stabilize these interactions. Additionally, computational methods—including molecular docking, molecular dynamics simulations, and machine learning pipelines—support predictions of lectin structures and binding properties, underpinning experimental efforts. These advanced techniques bring increased efficiency, accuracy, and a broader scope to lectin studies, with potential impacts across multiple fields. However, challenges such as data complexity and the need for experimental validation for computational methods remain. The future of lectin research will depend on the integration of these methods and the strengthening of interdisciplinarity to unlock the full potential of lectins.

Aqueous two-phase systems (ATPS) are an effective alternative method for partial or total purification of biomolecules. Using thermodynamic models to determine the liquid-liquid equilibrium activity coefficient in ATPS facilitates the process of obtaining new liquid-liquid equilibrium (LLE) data. Moreover, understanding the interactions that occur during protein transfer is crucial to optimize the application of ATPS in recovering valuable compounds. In this work, UNIFAC modeling of PEG and potassium phosphate-based ATPS was performed. The energy interaction parameters calculated from the interaction between the contribution groups present in the systems allowed a comprehensive study of the forces driving phase separation. Additionally, partition experiments were carried out to evaluate the ability of these ATPS to purify the rCabo lectin. The lectin showed a low interaction with the polymeric top phase and remained most concentrated at the interface. The thermodynamic partition parameters showed that the transference process becomes enthalpically driven as the temperature increases. Therefore, the present results allow for the estimation of new LLE data for ATPS formed by the same contribution groups, which can reduce the number of experiments and optimize the use of ATPS in the partitioning process.

Lectins are ubiquitous proteins that selectively bind to carbohydrates, serving as vital models for understanding protein-carbohydrate interactions. While extensively distributed across various life forms, plant lectins, especially from the Leguminosae family, have garnered significant attention. However, limited research exists on lectins from the Caesalpinioideae subfamily, suggesting a source of untapped biotechnological potential. This underscores the imperative for further exploration, particularly in isolating lectins from the Bauhinia genus, which remains relatively understudied, despite harboring lectins with diverse characteristics and promising biotechnological activities. In this study, a novel lectin extracted from Bauhinia catingae Harms seeds (BCL) was isolated in three chromatographic steps. BCL exhibited affinity for galactose and derivatives, akin to other Bauhinia lectins, with SDS-PAGE confirming its molecular weight around 30 kDa. Notably, BCL demonstrated stability across temperature and pH ranges and lacked metalloprotein characteristics. Electrospray ionization mass spectrometry revealed a partial sequence covering 81 % of the total protein sequence with nearly 80 % identity to Bauhinia forficata. Structural analysis suggested a β-sheet-rich secondary structure similar to that of other lectins. Further structural elucidation of BCL is essential to unveil its full potential and applications.

Lectins are proteins that recognize and bind to carbohydrates in a reversible and specific manner. In this work, a lectin from Crotalaria incana L. seeds was purified by Sephadex G-50 affinity chromatography. The purified lectin was named CiL and presented affinity towards D-mannose, D -glucose, D -galactose, alpha-methyl-D-mannoside and derivatives. CiL was stable over a wide range of temperatures and pH values, and it was divalent cation -dependent. SDS-PAGE analysis indicated that CiL is composed of two subunits with apparent masses of 29 and 30 kDa. The amino acid sequence of five tryptic peptides was obtained through mass spectrometry. Partial primary structure data indicated the similarity between CiL and lectins from Phaseolus vulgaris, Cladrastis kentukea, Lens culinaris, Pisum sativum, Crotalaria pallida and C. juncea. CiL showed no toxicity to Artemia salina nauplii at the concentration of 2 mg/mL, thus reinforcing the potential of this protein for further studies in other biological models and elucidation of possible effects.

The mechanisms behind Concanavalin A (ConA) circular permutation have been under investigation since 1985. Although a vast amount of information is available about this lectin and its applications, the exact purpose of its processing remains unclear. To shed light on this, this study employed computer simulations to compare the unprocessed ProConA with the mature ConA. This approach aimed to reveal the importance of the post-translational modifications, especially how they affect the lectin stability and carbohydrate-binding properties. To achieve these goals, we conducted 200 ns molecular dynamics simulations and trajectory analyses on the monomeric forms of ProConA and ConA (both unbound and in complex with D-mannose and the GlcNAc2Man9 N-glycan), as well as on their oligomeric forms. Our findings reveal significant stability differences between ProConA and ConA at both the monomeric and tetrameric levels, with ProConA exhibiting consistently lower stability parameters compared to ConA. In terms of carbohydrate binding properties, however, both lectins showed remarkable similarities in their interaction profiles, contact numbers, and binding free energies with D-mannose and the high-mannose N-glycan. Overall, our results suggest that the processing of ProConA significantly enhances the stability of the mature lectin, especially in maintaining the tetrameric oligomer, without substantially affecting its carbohydrate-binding properties.

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.

Understanding lectin-carbohydrate interactions at the structural and molecular levels is crucial to the field of lectins, as the diverse roles and biological activities exhibited by these proteins are fundamentally linked to their specific binding to target glycoconjugates. This study aimed to apply molecular dynamics to analyze the structure and binding properties of Parkia lectins. 3D structures of Parkia platycephala and P. biglobosa lectins, both unliganded and in complex with D-mannose, were used as inputs for simulations. The trajectories data enabled the study of stability, carbohydrate-binding interactions, and intermonomeric contacts for both proteins. The results revealed stable binding of D-mannose within the lectin domains and their binding mode at each of the three domains, displaying consistent binding motifs across the sites, with slight variations between the lectins and other Jacalin-related lectins. Despite these variations, the binding energies of the lectins with the ligand, as estimated using MM/GBSA, demonstrated favorable interactions in all cases. The dimeric interfaces of both lectins could be identified, and the main contacts have been mapped. These findings enhance our understanding of lectin-carbohydrate interactions and provide insights into the structural properties of Parkia lectins for potential biological and therapeutic applications.

Poor lifestyle choices and genetic predisposition are factors that increase the number of cancer cases, one example being breast cancer, the third most diagnosed type of malignancy. Currently, there is a demand for the development of new strategies to ensure early detection and treatment options that could contribute to the complete remission of breast tumors, which could lead to increased overall survival rates. In this context, the glycans observed at the surface of cancer cells are presented as efficient tumor cell markers. These carbohydrate structures can be recognized by lectins which can act as decoders of the glycocode. The application of plant lectins as tools for diagnosis/treatment of breast cancer encompasses the detection and sorting of glycans found in healthy and malignant cells. Here, we present an overview of the most recent studies in this field, demonstrating the potential of lectins as: mapping agents to detect differentially expressed glycans in breast cancer, as histochemistry/cytochemistry analysis agents, in lectin arrays, immobilized in chromatographic matrices, in drug delivery, and as biosensing agents. In addition, we describe lectins that present antiproliferative effects by themselves and/or in conjunction with other drugs in a synergistic effect.

As the main carbohydrate-binding proteins, lectins are responsible for several biological functions, although their specific roles are still being unveiled. In the current work, a jacalin-related lectin from the seeds of Parkia nitida (Fabaceae family, Mimosoideae subfamily) was isolated by a combination of saline precipitation, mannose affinity chromatography, and gel filtration chromatography. The lectin, henceforth designated as PNL, demon-strated remarkable similarity to other Parkia lectins at the biochemical and structural levels. Overall, PNL is a stable lectin with a molecular mass of 48,760.3 Da, composed of 451 amino acid residues that fold into 3 side-by -side & beta;-prism domains, each with its own carbohydrate-recognition domain specific to mannosides. Additionally, PNL displays a degree of toxicity against Artemia sp., albeit weaker than similar lectins. In conclusion, a representative of the Mimosoideae subfamily of legumes could be purified and characterized. This represents an advance in the understanding of Mimosoideae lectins, a group of unique proteins that receive significantly less focus in the plant lectin field.

Cells use glycans to encode information that modulates processes ranging from cell–cell recognition to programmed cell death. This information is encoded within a glycocode, and its decoding is performed by carbohydrate-binding proteins. Among these, lectins stand out due to their specific and reversible interaction with carbohydrates. Changes in glycosylation patterns are observed in several pathologies, including cancer, where abnormal glycans are found on the surfaces of affected tissues. Given the importance of the bioprospection of promising biomolecules, the current work aimed to determine the structural properties and anticancer potential of the mannose-specific lectin from seeds of Canavalia villosa (Cvill). Experimental elucidation of the primary and 3D structures of the lectin, along with glycan array and molecular docking, facilitated the determination of its fine carbohydrate-binding specificity. These structural insights, coupled with the lectin’s specificity, have been combined to explain the antiproliferative effect of Cvill against cancer cell lines. This effect is dependent on the carbohydrate-binding activity of Cvill and its uptake in the cells, with concomitant activation of autophagic and apoptotic pathways.

Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔѰm) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔѰm caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.

Glioblastoma multiforme (GBM) is the most aggressive type of glioma, displaying atypical glycosylation pattern that may modulate signaling pathways involved in tumorigenesis. Lectins are glycan binding proteins with antitumor properties. The present study was designed to evaluate the antitumor capacity of the Dioclea reflexa lectin (DrfL) on glioma cell cultures. Our results demonstrated that DrfL induced morphological changes and cytotoxic effects in glioma cell cultures of C6, U-87MG and GBM1 cell lines. The action of DrfL was dependent upon interaction with glycans, and required a carbohydrate recognition domain (CRD), and the cytotoxic effect was apparently selective for tumor cells, not altering viability and morphology of primary astrocytes. DrfL inhibited tumor cell migration, adhesion, proliferation and survival, and these effects were accompanied by activation of p38(MAPK) and JNK (p46/54), along with inhibition of Akt and ERK1/2. DrfL also upregulated pro-apoptotic (BNIP3 and PUMA) and autophagic proteins (Atg5 and LC3 cleavage) in GBM cells. Noteworthy, inhibition of autophagy and caspase-8 were both able to attenuate cell death in GBM cells treated with DrfL. Our results indicate that DrfL cytotoxicity against GBM involves modulation of cell pathways, including MAPKs and Akt, which are associated with autophagy and caspase-8 dependent cell death.