Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

{"title":"Loganic Acid Alleviates the Olfactory-Brain NLRP3 Inflammasome Activation and Rescues Dopaminergic Neurons in Experimental Models of Parkinson's Disease.","authors":"Samir Ranjan Panda, Pallabi Panja, Meenakshi Singh, Ujjawal Soni, Bishal Rajdev, Pankaj Garg, Sharad D Pawar, Rabinarayan Acharya, Anagha Ranade, V G M Naidu","doi":"10.1007/s11481-025-10183-9","DOIUrl":"https://doi.org/10.1007/s11481-025-10183-9","url":null,"abstract":"<p><p>The NLRP3 inflammasome signaling cascade activation is a significant contributor to the initiation and progression of Parkinson's disease (PD). Recent evidence supports that targeting NLRP3 inflammasome assembly could be a potential strategy to halt PD progression. The molecular mechanism of the olfactory-brain axis in mediating PD remains elusive. The current study explores that MPTP exposure to C57BL/6 mice leads to glial cell activation and impairs the olfactory function. The role of NLRP3 inflammasome activation in the olfactory bulb and the brain mediating neuroinflammation and neurodegeneration by activating multiple inflammatory pathways is explored. Loganic acid (LA), an iridoid glycoside, has been shown to provide antioxidant, anti-inflammatory, and inhibit microglial activation. Our results in-vitro studies demonstrated that LA treatment in MPP⁺-induced microglial cells inhibits NLRP3 inflammasome assembly, halts phagocytosis, and downregulates the release of pro-inflammatory cytokines such as IL-1β and IL-18. Further, results confirm that LA increases the neuronal differentiation markers and assists neurite growth. To correlate the in-vitro experiments with the in-vivo study, LA treatment prevented the loss of olfactory and motor function. In immunoblotting, LA treatment significantly inhibits the expression of NLRP3 inflammasome signaling cascade when compared to the MPTP group of the olfactory bulb and substantia nigra. Computational studies on LA on IL-β, NLRP3, caspase-1, and ASC also support strong evidence in the downregulation of inflammasome and cytokines through potential non-covalent interactions. The results confirm the neuroprotective effect of LA in PD by halting the NLRP3 inflammasome activation in the olfactory bulb and nigra region of the mice.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"19"},"PeriodicalIF":6.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of Neuroinflammation as a Common Mechanism of Action of Anorexigenic and Orexigenic Peptide Analogues in the Triple Transgenic Mouse Model of Alzheimer´s Disease.","authors":"Anna Mengr, Zuzana Šmotková, Andrea Pačesová, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská","doi":"10.1007/s11481-025-10174-w","DOIUrl":"https://doi.org/10.1007/s11481-025-10174-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia. Characterized by progressive neurodegeneration, AD typically begins with mild cognitive decline escalating to severe impairment in communication and responsiveness. It primarily affects cerebral regions responsible for cognition, memory, and language processing, significantly impeding the functional independence of patients. With nearly 50 million dementia cases worldwide, a number expected to triple by 2050, the need for effective treatments is more urgent than ever. Recent insights into the association between obesity, type 2 diabetes mellitus, and neurodegenerative disorders have led to the development of promising treatments involving antidiabetic and anti-obesity agents. One such novel promising candidate for addressing AD pathology is a lipidized analogue of anorexigenic peptide called prolactin-releasing peptide (palm¹¹-PrRP31). Interestingly, anorexigenic and orexigenic peptides have opposite effects on food intake regulation, however, both types exhibit neuroprotective properties. Recent studies have also identified ghrelin, an orexigenic peptide, as a potential neuroprotective agent. Hence, we employed both anorexigenic and orexigenic compounds to investigate the common mechanisms underpinning their neuroprotective effects in a triple transgenic mouse model of AD (3xTg-AD mouse model) combining amyloid-beta (Aβ) pathology and Tau pathology, two hallmarks of AD. We treated 3xTg-AD mice for 4 months with two stable lipidized anorexigenic peptide analogues - palm¹¹-PrRP31, and liraglutide, a glucagon-like peptide 1 (GLP-1) analogue - as well as Dpr³-ghrelin, a stable analogue of the orexigenic peptide ghrelin, and using the method of immunohistochemistry and western blot demonstrate the effects of these compounds on the development of AD-like pathology in the brain. Palm¹¹-PrRP31, Dpr³-ghrelin, and liraglutide reduced intraneuronal deposits of Aβ plaque load in the hippocampi and amygdalae of 3xTg-AD mice. Palm¹¹-PrRP31 and Dpr³-ghrelin reduced microgliosis in the hippocampi, amygdalae, and cortices of 3xTg-AD mice. Palm¹¹-PrRP31 and liraglutide reduced astrocytosis in the amygdalae of 3xTg-AD mice. We propose that these peptides are involved in reducing inflammation, a common mechanism underlying their therapeutic effects. This is the first study to demonstrate improvements in AD pathology following the administration of both orexigenic and anorexigenic compounds, highlighting the therapeutic potential of food intake-regulating peptides in neurodegenerative disorders.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"18"},"PeriodicalIF":6.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treg Upregulation by Treadmill Training Accelerates Myelin Repair Post-Ischemia.","authors":"Juan Zhong, Tao Liu, Yingxi He, Ying Zhu, Sen Li, Yuan Liu, Ce Yang, Lehua Yu, Lu Pan, Ying Yin, Botao Tan","doi":"10.1007/s11481-025-10178-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10178-6","url":null,"abstract":"<p><p>Regulatory T (Treg) cells contribute to white matter repair following ischemic stroke, but their limited availability in circulation restricts their therapeutic potential. Exercise, as a non-invasive and effective rehabilitation method, has been shown to restore Treg balance in diseases. This study explores the effects of treadmill training on Treg upregulation and its influence on myelin repair and functional recovery in rats with middle cerebral artery occlusion (MCAO). After four weeks of treadmill training, we analyzed the proportion of Treg cells (Tregs), FOXP3 expression, and oligodendrocyte-related protein levels using flow cytometry, immunofluorescence, and Western blotting. Myelin structure was examined with transmission electron microscopy (TEM), while motor coordination and balance were assessed using the fatigue rotarod and CatWalk analysis systems. To further explore the role of Tregs, the FOXP3 inhibitor P60 was used to inhibit Treg activity. The findings of our study indicate that training on a treadmill supports the maturation of oligodendrocytes, leads to an increase in myelin-associated proteins and the thickness of myelin, and promotes the recovery of motor function. Inhibition of Treg activity diminished these benefits, highlighting Tregs' key role in exercise-induced remyelination. These findings suggest that treadmill training facilitates myelin regeneration and functional recovery by upregulating Tregs, offering potential new strategies for stroke treatment.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"17"},"PeriodicalIF":6.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Chronic Binge Alcohol-Induced Hippocampal and Anterior Cingulate Cortex Neuroadaptations in Simian Immunodeficiency Virus (SIV)-Infected Female Rhesus Macaques.","authors":"Taylor Fitzpatrick-Schmidt, Amirsalar Mansouri, Jiri Adamec, Jennifer Klein, Larry Coleman, Kimberly N Edwards, Liz Simon, Patricia E Molina, Michael C Salling, Scott Edwards","doi":"10.1007/s11481-025-10179-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10179-5","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) infection produces neurological comorbidities including HIV-associated neurocognitive disorder (HAND) and chronic pain. HIV also increases the risk of developing an alcohol use disorder (AUD). With the rising prevalence of AUD in women and people with HIV (PWH), understanding the neurobiological impact of alcohol in these populations is important. We examined proteomic alterations in the hippocampus and anterior cingulate cortex (ACC), brain regions critical for cognition and affective pain, in a female rhesus macaque model of chronic binge alcohol administration and SIV infection. Adult female rhesus macaques received either chronic binge alcohol (CBA, 13-14 g/kg/week of alcohol) or water (VEH) via gastric catheter. All animals were inoculated with simian immunodeficiency virus (SIV_mac251) and treated with antiretroviral therapy (ART). Brain samples were processed for proteomic analysis, and quantitative discovery-based proteomics identified differentially expressed proteins in both brain regions comparing CBA treatment to VEH. Ingenuity Pathway Analysis (IPA) was also used to predict pathway activation. CBA significantly altered 147 proteins in the hippocampus and 176 proteins in the ACC. IPA revealed alterations in 39 canonical pathways in the hippocampus and 62 canonical pathways in the ACC. Fourteen common canonical pathways were enriched in both regions, including synaptogenesis and protein kinase A (PKA) signaling. These discoveries expand our understanding of how alcohol alters proteins of critical signaling pathways in vulnerable brain regions in the context of SIV/HIV infection and may lead to the development of new pharmacological treatment avenues for neurological dysfunction in women with HIV who use alcohol.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"16"},"PeriodicalIF":6.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer's Disease.","authors":"Anna Flavia Cantone, Chiara Burgaletto, Giulia Di Benedetto, Gabriella Gaudio, Cesarina Giallongo, Rosario Caltabiano, Giuseppe Broggi, Carlo Maria Bellanca, Giuseppina Cantarella, Renato Bernardini","doi":"10.1007/s11481-025-10177-7","DOIUrl":"10.1007/s11481-025-10177-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common cause of dementia worldwide, characterized by accumulation of amyloid-β protein and hyperphosphorylated tau protein in the brain. Neuroinflammation, resulting from chronic activation of brain-resident innate immune cells as well as enhanced peripheral leukocyte access across the blood-brain barrier, crucially affects AD progression. In this context, TNFSF10, a cytokine substantially expressed in the AD brain, has been shown to modulate both the innate and the adaptive branches of the immune response in AD-related neuroinflammation. In this study, we explored whether a TNFSF10-neutralizing treatment could represent a tool to re-balance the overall overshooting inflammatory response in a mouse model of AD. Specifically, 3xTg-AD mice were treated sub-chronically with an anti-TNFSF10 monoclonal antibody for three months, and were then sacrificed at 15 months. TNFSF10 neutralization reduced the expression of the inflammatory marker CD86, inversely related to levels of the anti-inflammatory marker CD206 in the brain of 3xTg-AD mice, suggesting a switch of microglia towards a neuroprotective phenotype. Similar results were observed in the splenic macrophage population. Moreover, flow cytometry revealed a significant decrease of CD4⁺CD25⁺FOXP3⁺ T regulatory cells as well as reduced number of CD11b⁺LY6C^high proinflammatory monocytes in both the brain and the spleen of 3xTg-AD mice treated with anti-TNFSF10 monoclonal antibody. Finally, the treatment resulted in lower count of splenic CD4⁺ and CD8⁺ T cells expressing PD1. The data suggest that TNFSF10 system-targeted treatment effectively restrain overshooting central and peripheral inflammation by rebalancing the overall immune response, mitigating the progression of AD pathology.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"15"},"PeriodicalIF":6.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKR Inhibition Prevents Neuroinflammation and Rescues Depressive-Like Behaviors via BDNF/TrkB Signaling.","authors":"Yue Hu, Tahir Ali, Shengnan Mou, Qichao Gong, Ruyan Gao, Yanhua Luo, Shupeng Li, Li Ling, Liangliang Hao","doi":"10.1007/s11481-025-10180-y","DOIUrl":"https://doi.org/10.1007/s11481-025-10180-y","url":null,"abstract":"<p><p>PKR, a kinase implicated in inflammation, accumulates in the brain, but its role in neuroinflammation-related depression is poorly understood. This study aimed to investigate whether pharmacological PKR inhibition using C16 (PKR inhibitor) could reverse LPS-induced neuroinflammation and depressive-like behaviors. Mice (C57BL/6J, 20-22 g, 6-8 weeks old) were administered LPS intraperitoneally for three days to induce depressive-like behavior and neuroinflammation. Simultaneously, mice were treated with C16 (a pharmacological PKR inhibitor) intraperitoneally for the same duration, followed by behavioral assessments. After euthanasia, brain-hippocampus tissues were collected for biochemical analysis. To validate these in vivo findings, BV2 and HT22 cells were cultured and subjected to pharmacological and biochemical analysis. LPS treatment significantly increased hippocampal neuroinflammation (GFAP/IBA-1 p < 0.001), cytokine production (IL-1β, IL-6, TNF-α, p < 0.05), PKR phosphorylation (p < 0.05), and inflammatory signaling (NLRP3/ASC, p < 0.001). Concomitantly, LPS exposure induced depressive-like symptoms (p < 0.001), impaired synaptic function (Synasin-1/SNAP25, p < 0.05), spine numbers (p < 0.001), and downregulated brain-derived neurotrophic factor (BDNF) /TrkB signaling (p < 0.001). Importantly, these effects were attenuated by C16, a PKR inhibitor. C16 also reduced LPS-induced ER stress markers in the hippocampus (p < 0.05). Interestingly, K252a, a BDNF/TrkB inhibitor, reversed the protective effects of C16, increasing both neuroinflammation (p < 0.001) and depressive symptoms (p < 0.001) in LPS-treated mice. Notably, in vitro studies using BV2 and HT22 cells corroborated these findings. In conclusion, these findings suggest that PKR is critical in mediating LPS-induced neuroinflammation and depressive-like behaviors, potentially through interactions with BDNF/TrkB signaling.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"13"},"PeriodicalIF":6.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Perspective on Mechanisms of Neurodegeneration in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: the Early and Critical Role of Platelets in Neuro/Axonal Loss.","authors":"Jacqueline Monique Orian","doi":"10.1007/s11481-025-10182-w","DOIUrl":"10.1007/s11481-025-10182-w","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder, with limited treatment options. This disease is characterized by differential pathophysiology between grey matter (GM) and white matter (WM). The predominant WM hallmark is the perivascular plaque, associated with blood brain barrier (BBB) loss of function, lymphocytic infiltration, microglial reactivity, demyelination and axonal injury and is adequately addressed with immunomodulatory drugs. By contrast, mechanisms underlying GM damage remain obscure, with consequences for neuroprotective strategies. Cortical GM pathology is already significant in early MS and characterized by reduced BBB disruption and lymphocytic infiltration relative to WM, but a highly inflammatory environment, microglial reactivity, demyelination and neuro/axonal loss. There is no satisfactory explanation for the occurrence of neurodegeneration without large-scale inflammatory cell influx in cortical GM. A candidate mechanism suggests that it results from soluble factors originating from meningeal inflammatory cell aggregates, which diffuse into the underlying cortical tissue and trigger microglial activation. However, the recent literature highlights the central role of platelets in inflammation, together with the relationship between coagulation factors, particularly fibrinogen, and tissue damage in MS. Using the experimental autoimmune encephalomyelitis (EAE) model, we identified platelets as drivers of neuroinflammation and platelet-neuron associations from the pre-symptomatic stage. We propose that fibrinogen leakage across the BBB is a signal for platelet infiltration and that platelets represent a major and early participant in neurodegeneration. This concept is compatible with the new appreciation of platelets as immune cells and of neuronal damage driven by inflammatory cells sequestered in the meninges.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"14"},"PeriodicalIF":6.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review.","authors":"Eman A Alraddadi, Faisal F Aljuhani, Ghadah Y Alsamiri, Salwa Y Hafez, Ghaida Alselami, Daniyah A Almarghalani, Faisal F Alamri","doi":"10.1007/s11481-025-10171-z","DOIUrl":"10.1007/s11481-025-10171-z","url":null,"abstract":"<p><p>Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is interrupted, reducing the blood supply to the affected area. Inflammation is a significant component in stroke pathophysiology. Neuroinflammation is triggered following the acute ischemic ictus, where the blood-brain barrier (BBB) breaks down, causing damage to the endothelial cells. The damage will eventually generate oxidative stress, activate the pathological phenotypes of astrocytes and microglia, and lead to neuronal death in the neurovascular unit. As a result, the brain unleashes a robust neuroinflammatory response, which can further worsen the neurological outcomes. Neuroinflammation is a complex pathological process involved in ischemic damage and repair. Finding new neuroinflammation molecular targets is essential to develop effective and safe novel treatment approaches against ischemic stroke. Accumulating studies have investigated the pharmacological properties of cannabinoids (CBs) for many years, and recent research has shown their potential therapeutic use in treating ischemic stroke in rodent models. These findings revealed promising impacts of CBs in reducing neuroinflammation and cellular death and ameliorating neurological deficits. In this review, we explore the possibility of the therapeutic administration of CBs in mitigating neuroinflammation caused by a stroke. We summarize the results from several preclinical studies evaluating the efficacy of CBs anti-inflammatory interventions in ischemic stroke. Although convincing preclinical evidence implies that CBs targeting neuroinflammation are promising for ischemic stroke, translating these findings into the clinical setting has proven to be challenging. The translation hurdle is due to the essence of the CBs ability to cause anxiety, cognitive deficit, and psychosis. Future studies are warranted to address the dose-beneficial effect of CBs in clinical trials of ischemic stroke-related neuroinflammation treatment.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"12"},"PeriodicalIF":6.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NXP032 Improves Memory Impairment Through Suppression of Tauopathy in PS19 Mice and Attenuates Okadaic Acid-Induced Tauopathy in SH-SY5Y Cells.","authors":"Hyeyoon Eo, Seong Hye Kim, In Gyoung Ju, Joo Hee Lee, Myung Sook Oh, Youn-Jung Kim","doi":"10.1007/s11481-025-10175-9","DOIUrl":"https://doi.org/10.1007/s11481-025-10175-9","url":null,"abstract":"<p><p>Tauopathy is widely observed in multiple neurodegenerative diseases such as Alzheimer's disease (AD) and characterized by abnormal tau protein phosphorylation, aggregation and its accumulation as a form of neurofibrillary tangle (NFT) in the brain. However, there are no effective treatments targeting tau pathology in the AD. Vitamin C is known to reduce tauopathy and modulate one of its regulators called glycogen synthase kinase 3 (GSK3) in the body. Nevertheless, vitamin C has a limitation of its stability during metabolism due to its chemical properties. Thus, in the current study, NXP032 (a vitamin C/aptamer complex) was tested as a candidate for tau-targeting treatment because it can preserve antioxidative efficacy of vitamin C before it can reach the target tissue. In this context, the current study aimed to investigate the therapeutic effect of NXP032 on tauopathy in vivo and in vitro. As a result, NXP032 attenuated cognitive and memory decline and reduced NFT and tau hyperphosphorylation in the P301S mutant human tau transgenic mice (or called PS19 mice). In addition, NXP032 suppressed neuroinflammation found in the PS19 mice. Furthermore, NXP032 protected SH-SY5Y human neuroblastoma cells from okadaic acid (OKA)-induced cytotoxicity. Especially, 10 ng/ml of NXP032 reduced tau hyperphosphorylation and GSK3 activation though its phosphorylation at Tyr216 site which were promoted by OKA treatment in the SH-SY5Y cells. Taken together, our results suggest that NXP032 might be a potential therapy for AD and tauopathy-related neurodegenerative disorders as well.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"10"},"PeriodicalIF":6.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Study of Nanoconjugates of a Synthetic and a Natural Drug Against T2DM-Induced Cognitive Dysfunction.","authors":"Sweta Priyadarshini Pradhan, Anindita Behera, Pratap Kumar Sahu","doi":"10.1007/s11481-025-10170-0","DOIUrl":"https://doi.org/10.1007/s11481-025-10170-0","url":null,"abstract":"<p><p>Type II Diabetes Mellitus (T2DM) is one of the risk factors for the development of dementia leading to cognitive dysfunctions. The present study evaluates the efficacy of a synthetic drug (Vildagliptin, VLD) and a natural glycosidic compound (Hesperidin, HSP) against T2DM-induced cognitive dysfunction in rats. The drugs were conjugated with metal nanoparticles like gold (Au) and selenium (Se) to enhance their efficacy. The synthesis of the monometallic and bimetallic nanoparticles of VLD and HSP was established via the turkevich method and characterised by different spectroscopical techniques like UV (Ultraviolet)-visible, FTIR (Fourier Transform Infrared Spectroscopy), zeta potential, particle size, HR-TEM (High Resolution Transmission Electron Microscopy), SAED (Selected Area Electron Diffraction) and SEM-EDX (Scanning Electron Microscopy with Energy Dispersive X-ray Analysis). Both Streptozotocin (STZ) of 65 mg/kg (Group I-X) and Alloxan (ALX) of 150 mg/kg (Group I-X) were injected into 120 Wistar rats to induce cognitive dysfunction. After the induction, the BGL levels were evaluated and rats with BGL > 250 mg/dl were used in the study. Then the test drug and nanoformulations were administered for 21 days. Neurobehavioral assessment, antioxidant studies, and estimation of AChE (acetylcholinesterase) and nitrite levels were done. The VLD and HSP with its nanoconjugates significantly attenuated the effect of STZ and ALX by improving the memory and learning function in Y-maze, radial arm maze (RAM), and elevated plus maze (EPM), increased antioxidant levels of SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione); decreased lipid peroxidation and reduced the AChE and nitrite levels in the rat brain. The bimetallic nanoconjugates of both VLD and HSP were more effective than the monometallic forms of VLD and HSP. However, VLD and its nanoconjugates exhibited better neuroprotective activity than HSP and its nanoconjugates in STZ and ALX animal models. VLD and its nanoformulations were more effective against long-term memory than HSP and its nanoconjugates. Both VLD and HSP may be a potential lead for cognitive and neurodegenerative diseases.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"11"},"PeriodicalIF":6.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}