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Yuvaraj Manoharan,1,* Qingmin Ji,2,* Tomohiko Yamazaki,2,3 Shanmugavel Chinnathambi,1 Song Chen,2,4 Ganesan Singaravelu,1 Jonathan P Hill,2 Katsuhiko Ariga,2,5 Nobutaka Hanagata3,6 1Department of Medical Physics, Anna University, Chennai, India; 2Research Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibarak, 3Graduate School of Life Science, Hokkaido University, Kita-ku, Sapporo, 4JSPS Research Fellow, Chiyoda-ku, Tokyo, 5JST and CREST, National Institute for Materials Science, Tsukuba, Ibaraki, Japan; 6Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Ibaraki, Japan*These authors contributed equally to this workBackground: Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules.Methods: For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO2 nanoparticles were prepared by coating SiO2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da).Results: The capacity of the flake-shell SiO2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.Keywords: CpG oligodeoxynucleotides, polyethyleneimine, Toll-like receptor 9, silica nanoparticles, delivery, interferon-α

In this work, we have fabricated a new electrochemical sensor based on β‐tricalcium phosphate (Ca3(PO4)2) nanoparticles (NPs) modified glassy carbon electrode (GCE) for the selective nonenzymatic determination of methyl parathion and mercury (II) ions independently. β‐tricalcium phosphate (β‐TCP) NPs were prepared by chemical precipitation method and structural and morphological properties were investigated by XRD, FTIR, and SEM. The electrochemical behavior of MP and mercury (Hg2+) ions were investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques using β‐TCP/GCE. The modified electrode exhibited excellent electrocatalytic activity towards both the MP and Hg over a wide linear range from 0.15 to 141 μM and 1–381 µM with the lowest detection limits of 88 and 136.4 nM respectively. The sensor has high selectivity towards MP and Hg in the presence of major interfering compounds such as 3-nitrophenol, 4-nitrophenol, 4-aminophenol, catechol, hydroquinone and heavy metals such as lead, cadmium and arsenic. Applicability of the fabricated sensor for detection of MP and Hg (II) ions has been tested in tap water by standard addition method.

Pure, mixed and doped metal oxides (MOX) have attracted great interest for the development of electrical and electrochemical sensors since they are cheaper, faster, easier to operate and capable of online analysis and real-time identification. This review focuses on highly sensitive chemoresistive type sensors based on doped-SnO2, RhO, ZnO-Ca, Smx-CoFe2−xO4 semiconductors used to detect toxic gases (H2, CO, NO2) and volatile organic compounds (VOCs) (e.g., acetone, ethanol) in monitoring of gaseous markers in the breath of patients with specific pathologies and for environmental pollution control. Interesting results about the monitoring of biochemical substances as dopamine, epinephrine, serotonin and glucose have been also reported using electrochemical sensors based on hybrid MOX nanocomposite modified glassy carbon and screen-printed carbon electrodes. The fundamental sensing mechanisms and commercial limitations of the MOX-based electrical and electrochemical sensors are discussed providing research directions to bridge the existing gap between new sensing concepts and real-world analytical applications.

The room-temperature synthesis of silver (AgNPs) and gold (AuNPs) nanoparticles from aqueous solution of AgNO3 and HAuCl4 respectively, using Rumex roseus (RR) plant extract as a reducing agent, is reported here for the first time. The nanoparticles obtained were characterized by UV-Vis spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS). The formation of nanoparticles with spherical-shaped morphology was verified by TEM and confirmed by UV-Vis spectroscopy through the analysis of Ag and Au plasmon resonance peak and DLS measurements. New electrochemical sensors have been developed by employing the synthesized Ag and Au nanoparticles as modifiers of glassy carbon electrode (GCE) and screen-printed carbon electrode (SPCE), respectively. The AgNPs-modified GCE was investigated for the electrochemical determination of hydrogen peroxide (H2O2). Further enhancement of electrochemical performances was obtained using a nanocomposite made of AgNPs and reduced graphene oxide (rGO)-modified GCE. The AuNPs-SPCE sensor was instead tested in the electrochemical sensing of riboflavin (RF). To our knowledge, this is the first paper reporting Rumex roseus plant extract as a source for the synthesis of metal nanoparticles and their use for developing simple, sensitive and reliable electrochemical sensors for H2O2 and RF.

A marine ascidian-associated bacterium, Halobacillus trueperi RSK CAS9, was optimized for lipase production by response surface methodology using marine waste as substrate. The central composite design was employed, and the optimal medium constituents for maximum lipase production (1355.81 U/ml) were determined to be tuna powder (14.58 g/l), olive oil (5.05 ml/l); NaCl (72.42 g/l), temperature (45 °C) and pH 9.0. An alkaline lipase was purified to 8.46 fold with 1193.59 U mg−1 specific activities with the molecular weight of 44 kDa. The activity was substantially inhibited by EDTA and PMSF, indicating that it was a metalloenzyme serine residue which was essential for catalytic activity. Thus, lipase production by microbial conversion of marine fish wastes in this study suggested its potential utilization for the production of high value products.

Sensing properties of chemical sensors based on ternary hydroxyapatite-graphene-multiwalled carbon nanotube (HA-GN-MWCNT) nanocomposite in the detection of chemical substances representing risk factors for sudden infant death syndrome (SIDS), have been evaluated. Characterization data of the synthesized composite have shown that the graphene-MWCNT network serves as a matrix to uniformly disperse the hydroxyapatite nanoparticles and provide suitable electrical properties required for developing novel electrochemical and conductometric sensors. A HA-GN-MWCNT composite-modified glassy carbon electrode (HA-GN-MWCNT/GCE) has been fabricated and tested for the simultaneous monitoring of nicotine and caffeine by cyclic voltammetry (CV) and square wave voltammetry (SWV), whereas a HA-GN-MWCNT conductive gas sensor has been tested for the detection of CO2 in ambient air. Reported results suggest that the synergic combination of the chemical properties of HA and electrical/electrochemical characteristics of the mixed graphene-MWCNT network play a prominent role in enhancing the electrochemical and gas sensing behavior of the ternary HA-GN-MWCNT hybrid nanostructure. The high performances of the developed sensors make them suitable for monitoring unhealthy actions (e.g., smoking, drinking coffee) in breastfeeding women and environmental factors (bad air quality), which are associated with an enhanced risk for SIDS.

The Flowering Locus T1 (FT1) gene from Populus trichocarpa under the control of the 35S promoter was transformed into European plum (Prunus domestica L). Transgenic plants expressing higher levels of FT flowered and produced fruits in the greenhouse within 1 to 10 months. FT plums did not enter dormancy after cold or short day treatments yet field planted FT plums remained winter hardy down to at least -10°C. The plants also displayed pleiotropic phenotypes atypical for plum including shrub-type growth habit and panicle flower architecture. The flowering and fruiting phenotype was found to be continuous in the greenhouse but limited to spring and fall in the field. The pattern of flowering in the field correlated with lower daily temperatures. This apparent temperature effect was subsequently confirmed in growth chamber studies. The pleitropic phenotypes associated with FT1 expression in plum suggests a fundamental role of this gene in plant growth and development. This study demonstrates the potential for a single transgene event to markedly affect the vegetative and reproductive growth and development of an economically important temperate woody perennial crop. We suggest that FT1 may be a useful tool to modify temperate plants to changing climates and/or to adapt these crops to new growing areas.

Activity of α- l-arabinofuranosidae (EC 3.2.1.55) ranged between 0.03 and 1.63 U/ml when Sclerotium rolfsii was grown in a synthetic medium containing different nitrogen and carbon sources. Agricultural and forest residues such as rice straw, corn cob, groundnut husk, and apple pomace were suitable substrates for enzyme production. Maximum activity, 4.2 U/ml, was with pre-treated corn cobs. [ABSTRACT FROM AUTHOR]

Structural DNA nanotechnology is an emerging field and is expected to be used for various applications in materials science. In this study, we designed a DNA tensegrity triangle to accommodate the bipyridine complexes with metal ions (Ni 2+ and Fe 2+ ) at the center of the space within the triangle. A metal-bipyridine-incorporated DNA tensegrity triangle was crystalized, and the presence of metals within it was confirmed through X-ray crystal structure analysis. A signal of the anomalous dispersion effect derived from metal was observed in the center of the DNA triangle.

Ten macrocyclic peptides, each comprising 14 amino acids, were designed and synthesized based on the Tau aggregation model hexapeptides AcPHF6* and AcPHF6. The design took into account the aggregation tendencies of each residue in AcPHF6* and AcPHF6, their aggregation models, while employing peptide-based structural design principles including N-methylation to promote turns and to block hydrogen bond propagation and elongation of the aggregation chain. NMR analysis supported that all these peptides adopted an antiparallel β-sheet conformation. Self-aggregation studies characterized the aggregation properties of these peptides, identifying two peptides with the highest (P3) and lowest (P8) aggregation tendencies. In cross-aggregation studies with the parent peptides AcPHF6* and AcPHF6, P3 and P8 were found to promote and reduce aggregation, respectively. Furthermore, P3 and P8 demonstrated an enhancement and diminution effect on the aggregation of K18wt, indicating their capacity to modulate aggregation even at the macromolecular level. Thus, the two simple peptides, P3 and P8 selectively exhibit pro- or anti-aggregation effects on PHF peptides and Tau. This study, has thus developed structurally well-defined non-complex peptides, derived from AcPHF6* and AcPHF6, to modulate Tau aggregation as desired, offering applications in Tau model studies and the development of Tau aggregation inhibitors or promoters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for cancer treatment due to their unique properties. Featuring high porosity, extensive surface area, chemical stability, and good biocompatibility, MOFs are ideal for efficient drug delivery, targeted therapy, and controlled release. They can be designed to target specific cellular organelles to disrupt metabolic processes in cancer cells. Additionally, functionalization with enzymes mimics their catalytic activity, enhancing photodynamic therapy and overcoming apoptosis resistance in cancer cells. The controllable and regular structure of MOFs, along with their tumor microenvironment responsiveness, make them promising nanocarriers for anticancer drugs. These carriers can effectively deliver a wide range of drugs with improved bioavailability, controlled release rate, and targeted delivery efficiency compared to alternatives. In this article, we review both experimental and computational studies focusing on the interaction between MOFs and drug, explicating the release mechanisms and stability in physiological conditions. Notably, we explore the relationship between MOF structure and its ability to damage cancer cells, elucidating why MOFs are excellent candidates for bio-applicability. By understanding the problem and exploring potential solutions, this review provides insights into the future directions for harnessing the full potential of MOFs, ultimately leading to improved therapeutic outcomes in cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shano, Karthikeyan, Kennedy, Chinnathambi and Pandian.)

Quantum dots, which won the Nobel Prize in Chemistry, have recently gained significant attention in precision medicine due to their unique properties, such as size-tunable emission, high photostability, efficient light absorption, and vibrant luminescence. Consequently, there is a growing demand to identify new types of quantum dots from various sources and explore their potential applications as stimuli-responsive biosensors, biomolecular imaging probes, and targeted drug delivery agents. Biomass-waste-derived carbon quantum dots (CQDs) are an attractive alternative to conventional QDs, which often require expensive and toxic precursors, as they offer several merits in eco-friendly synthesis, preparation from renewable sources, and cost-effective production. In this study, we evaluated three CQDs derived from biomass waste for their potential application as non-toxic bioimaging agents in various cell lines, including human dermal fibroblasts, HeLa, cardiomyocytes, induced pluripotent stem cells, and an in-vivo medaka fish (Oryzias latipes) model. Confocal microscopic studies revealed that CQDs could assist in visualizing inflammatory processes in the cells, as they were taken up more by cells treated with tumor necrosis factor-α than untreated cells. In addition, our quantitative real-time PCR gene expression analysis has revealed that citric acid-based CQDs can potentially reduce inflammatory markers such as Interleukin-6. Our studies suggest that CQDs have potential as theragnostic agents, which can simultaneously identify and modulate inflammatory markers and may lead to targeted therapy for immune system-associated diseases., (© 2024. The Author(s).)

Toll-like receptor 9 (TLR-9) is a protein that helps our immune system identify specific DNA types. Upon detection, CpG oligodeoxynucleotides signal the immune system to generate cytokines, essential proteins that contribute to the body's defence against infectious diseases. Native phosphodiester type B CpG ODNs induce only Interleukin-6 with no effect on interferon-α. We prepared silicon quantum dots containing different surface charges, such as positive, negative, and neutral, using amine, acrylate-modified Plouronic F-127, and Plouronic F-127. Then, class B CpG ODNs are loaded on the surface of the prepared SiQDs. The uptake of ODNs varies based on the surface charge; positively charged SiQDs demonstrate higher adsorption compared to SiQDs with negative and neutral surface charges. The level of cytokine production in peripheral blood mononuclear cells was found to be associated with the surface charge of SiQDs prior to the binding of the CpG ODNs. Significantly higher levels of IL-6 and IFN-α induction were observed compared to neutral and negatively charged SiQDs loaded with CpG ODNs. This observation strongly supports the notion that the surface charge of SiQDs effectively regulates cytokine induction., (© 2024. The Author(s).)

Environmental endocrine-disrupting chemicals, Bisphenol A (BPA) and 4-Nitrophenol (4-NP), pose significant risks to reproductive health in both animals and humans. Here, we introduce the first utilization of the 4-leg spin ladder compound La 2 Cu 2 O 5 as an electrode material for electrochemical sensor. Nanostructured La 2 Cu 2 O 5 was synthesized via a straightforward Sol-Gel method and thoroughly characterized using X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, and powder X-ray diffraction. La 2 Cu 2 O 5 nanoparticles modified glassy carbon electrode (GCE) exhibited a significant electrocatalytic activity towards the oxidation of BPA and 4-NP in phosphate buffer saline (pH 7.0). Square wave voltammetry studies revealed lowest detection limits of 3 nM for BPA and 2.6 nM for 4-NP over a wider concentration range of 0.01-500 μM. Notably, this study marks the first utilization of La 2 Cu 2 O 5 for simultaneous electrochemical detection of BPA and 4-NP, demonstrating its potential in this field. Furthermore, the sensor exhibited good sensitivity, reproducibility, and selectivity towards BPA and 4-NP, even in the presence of similar potential organic and inorganic interferents. Additionally, the newly developed sensor enabled simultaneous quantification of BPA and 4-NP in real samples such as packaged milk, river water, and plastic bottles, achieving recovery rates above 95%. Importantly, our results underscore the leaching of BPA into water from thin and thick plastics at elevated temperatures (40 °C-80 °C), emphasizing the utility of the proposed sensor for rapid and simultaneous detection of BPA and 4-NP in environmental and food matrices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:C. Sekar reports financial support was provided by Inter-University Accelerator Centre. C.Sekar reports financial support was provided by National Higher Education Mission., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transcription therapy is an emerging approach that centers on identifying the factors associated with the malfunctioning gene transcription machinery that causes diseases and controlling them with designer agents. Until now, the primary research focus in therapeutic gene modulation has been on small-molecule drugs that target epigenetic enzymes and critical signaling pathways. However, nucleic acid-based small molecules have gained popularity in recent years for their amenability to be pre-designed and realize operative control over the dynamic transcription machinery that governs how the immune system responds to diseases. Pyrrole-imidazole polyamides (PIPs) are well-established DNA-based small-molecule gene regulators that overcome the limitations of their conventional counterparts owing to their sequence-targeted specificity, versatile regulatory efficiency, and biocompatibility. Here, we emphasize the rational design of PIPs, their functional mechanisms, and their potential as targeted transcription therapeutics for disease treatment by regulating the immune response. Furthermore, we also discuss the challenges and foresight of this approach in personalized immunotherapy in precision medicine., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Viral infections cause significant health problems all over the world, and it is critical to develop treatments for these problems. Antivirals that target viral genome-encoded proteins frequently cause the virus to become more resistant to treatment. Because viruses rely on several cellular proteins and phosphorylation processes that are essential to their life cycle, drugs targeting host-based targets could be a viable treatment option. To reduce costs and improve efficiency, existing kinase inhibitors could be repurposed as antiviral medications; however, this method rarely works, and specific biophysical approaches are required in the field. Because of the widespread use of FDA-approved kinase inhibitors, it is now possible to better understand how host kinases contribute to viral infection. The purpose of this article is to investigate the tyrphostin AG879 (Tyrosine kinase inhibitor) binding information in Bovine Serum Albumin (BSA), human ErbB2 (HER2), C-RAF1 Kinase (c-RAF), SARS-CoV-2 main protease (COVID 19), and Angiotensin-converting enzyme 2 (ACE-2).Communicated by Ramaswamy H. Sarma.

Pectin is a polysaccharide mainly used in food processing industries as an emulsifier, thickener, stabilizer and in pharmaceuticals as an excipient, wall material and bio adhesive for improving delivery and efficiency. Raising demand for pectin, pushes to explore unconventional plant-based sources for the extraction of pectin. This work is aimed to explore the possibility of extracting pectin from the peel of banana varieties and to decipher the chemical and techno-functional properties. Among the varieties, Nendran, a plantain banana recorded higher pectin recovery (23.42 %), swelling power (23.10 gg -1 ), anhydrouronic acid (AUA) content (72.86 %) and emulsifying activity (46.19 %). Pectin from the banana peels exhibited the equivalent weight (g/mol) ranging from 943.40 (var. Bhimkol) to 1282.05 (var. Nendran). Morphological observations revealed that the extracted pectin has fragments with uneven sizes and inter-particle voids in the structure. Banana pectin behaved similar to commercial pectin in terms of rheological, textural and structural profiles. HPLC analysis and NMR spectra confirmed the dominance of galacturonic acid in the banana peel pectins. The study unveiled and opened up the avenues of utilizing banana peel as a complementary biomass for the extraction of pectin which could be used in different industrial applications., Competing Interests: Declaration of competing interest Paramasivam Suresh kumar reports financial support was provided by Indian Council of Agricultural Research., (Copyright © 2023. Published by Elsevier B.V.)

Chalcone derivatives are an extremely valuable class of compounds, primarily due to the keto-ethylenic group, CO-CH[double bond, length as m-dash]CH-, they contain. Moreover, the presence of a reactive α,β-unsaturated carbonyl group confers upon them a broad range of pharmacological properties. Recent developments in heterocyclic chemistry have led to the synthesis of chalcone derivatives, which have been biologically investigated for their activity against certain diseases. In this study, we investigated the binding of new chalcone derivatives with COX-2 (cyclooxygenase-2) and HSA (Human Serum Albumin) using spectroscopic and molecular modeling studies. COX-2 is commonly found in cancer and plays a role in the production of prostaglandin E (2), which can help tumors grow by binding to receptors. HSA is the most abundant protein in blood plasma, and it transports various compounds, including hormones and fatty acids. The conformation of chalcone derivatives in the HSA complex system was established through fluorescence steady and excited state spectroscopy techniques and FTIR analyses. To gain a more comprehensive understanding, molecular docking, and dynamics were conducted on the target protein (COX-2) and transport protein (HSA). In addition, we conducted density-functional theory (DFT) and single-point DFT to understand intermolecular interaction in protein active sites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cytoskeletal dysregulation forms an important aspect of many neurodegenerative diseases such as Alzheimer's disease. Cytoskeletal functions require the dynamic activity of the cytoskeletal proteins-actin, tubulin, and the associated proteins. One of such important phenomena is that of actin remodeling, which helps the cell to migrate, navigate, and interact with extracellular materials. Podosomes are complex actin-rich cytoskeletal structures, abundant in proteins that interact and degrade the extracellular matrix, enabling cells to displace and migrate. The formation of podosomes requires extensive actin networks and remodeling. Here we present a novel immunofluorescence-based approach to study actin remodeling in neurons through the medium of podosomes., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is distinguished by extracellular accumulation of amyloid-beta plaques and intracellular neurofibrillary tangles of Tau. Pathogenic Tau species are also known to display "prion-like propagation," which explains their presence in extracellular spaces as well. Glial population, especially microglia, tend to proclaim neuroinflammatory condition, disrupted signaling mechanisms, and cytoskeleton deregulation in AD. Omega-3 fatty acids play a neuroprotective role in the brain, which can trigger the anti-inflammatory pathways as well as actin dynamics in the cells. Improvement of cytoskeletal assembly mechanism by omega-3 fatty acids would regulate the other signaling cascades in the cells, leading to refining clearance of extracellular protein burden in AD. In this study, we focused on analyzing the ability of α-linolenic acid (ALA) as a regulator of actin dynamics to balance the signaling pathways in microglia, including endocytosis of extracellular Tau burden in AD., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease, a progressive neurological disorder, is characterized by the accumulation of neurofibrillary tangles and senile plaques by Tau and amyloid-β, respectively, in the brain microenvironment. The misfolded protein aggregates interact with several components of neuronal and glial cells such as membrane lipids, receptors, transporters, enzymes, cytoskeletal proteins, etc. Under pathological conditions, Tau interacts with several G-protein-coupled receptors (GPCRs), which undergoes either receptor signaling or desensitization followed by internalization of the protein complex. The purinergic GPCR, P2Y12 which is expressed in microglial cells, plays a key role in its activation and migration. Microglial cells sense and migrate to the site of injury aided by P2Y12 receptor that interacts with ADP released from damaged cells. P2Y12 receptor also interacts with misfolded Tau accumulated at the extracellular space and promotes receptor-mediated internalization. Immunocolocalization and co-immunoprecipitation studies demonstrated the interaction of Tau species with the P2Y12 receptor. Later, in-silico analyses were carried out with the repeat domain of Tau (Tau RD ), which has been identified as the interacting partner of P2Y12 receptor by in-vitro studies. Molecular docking and molecular dynamics simulation studies show the stability and the type of interaction in Tau RD -receptor complex. Tau interaction with P2Y12 receptor plays a significant role in maintaining the active state of microglia which could lead to neuroinflammation and neuronal damage in AD brain. Hence, blocking P2Y12-Tau interaction and P2Y12-mediated Tau internalization in microglial cells could be possible therapeutic strategies in downregulating the severity of neuroinflammation in AD., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

In Alzheimer's disease, the synaptic loss is prominent due to the accumulation of Amyloid βeta (Aβ) protein in synapses, which affect neurotransmission, and thus ultimately causes neuronal loss. Tau, a microtubule-associated protein, is a vital protein of intracellular neurofibrillary tangles (NFTs) in AD. Along with the accumulation of aberrant proteins, glial cells, mainly astrocytes and microglia, play a major role in impairing neuronal network. Microglia have the ability to phagocytose Tau and rerelease in exosomes, which causes further spreading of Tau. Reduction in exosome synthesis can reduce spreading of Tau. Modulating microglia to clear the extracellular Tau seeds by its imported degradation would resolve the disease condition in Alzheimer's disease. In this study, we have shown the ability of α-linolenic acid (ALA) to inhibit the Tau aggregation and modulate their internalization property in microglial cells., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)