Inflammopharmacology最新文献

{"title":"Intact glycoconjugates from Taenia crassiceps excreted/secreted products ameliorate chemically induced colitis by modulating inflammation and strengthening adherens junctions.","authors":"Yadira Ledesma-Soto, Ilse Chávez-Soto, Marissa Calderón-Torres, Andrea Monserrat Rodríguez-Lozoya, Jonadab E Olguin, Luis B Hernández-Portilla, César M Flores-Ortíz, Fernando Candanedo, Miriam Rodriguez-Sosa, Sonia E Hernández-Navia, Luis I Terrazas","doi":"10.1007/s10787-025-01821-y","DOIUrl":"https://doi.org/10.1007/s10787-025-01821-y","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence worldwide. Notably, helminth infections, known for their immunoregulatory properties, are inversely related to inflammatory conditions such as UC. Research has indicated that Taenia crassiceps infection can improve inflammatory-mediated diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and colitis. Subsequent studies revealed that helminth-derived products can replicate the effects of complete infection in the context of inflammatory diseases; however, the mechanisms underlying these effects remain unclear. This study examined the impact of intact glycans from T. crassiceps excreted/secreted products (TcES) on host responses to dextran sodium sulfate (DSS)-induced colitis.</p><p><strong>Methods: </strong>UC was induced by administering 4% DSS in the drinking water for 9 days. The mice were treated with intact TcES, glycan-depleted TcES, or protein-depleted TcES 2 days after colitis induction. Symptoms of the disease, along with immunologic and histopathological evaluations, were performed.</p><p><strong>Results: </strong>Colitic mice that received intact TcES presented fewer disease symptoms and less histopathological damage. Intact TcES reduced the proinflammatory response while increasing the production of IL-4, IL-22, IL-31, and MCP-1 and promoting M2 macrophage polarization via PD-L2 expression. Furthermore, intact TcES diminished neutrophil infiltration, inhibited NF-κB and p38 phosphorylation in the colon, and suppressed reactive oxygen species and 3-nitrotyrosine levels, thus protecting the colon. These effects were accompanied by increased expression of E-cadherin and β-catenin, indicating improved epithelial barrier integrity. Conversely, mice treated with glycan-depleted or protein-depleted TcES exhibited exacerbated colitis characterized by disruption of colon tissue architecture, extensive inflammation, and epithelial damage, including loss of E-cadherin and β-catenin and a lack of M2 macrophage polarization.</p><p><strong>Conclusions: </strong>Glycoconjugates on TcES play a significant role in mediating the immunomodulatory effects that alleviate DSS-induced colitis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation and metabolic dysregulation as predictors of cognitive impairment, depression, and quality of life in type 2 diabetes mellitus patients on SGLT2 inhibitors and sulfonylureas.","authors":"Haya Majid, Sajad Ul Islam, Sunil Kohli, Nidhi","doi":"10.1007/s10787-025-01824-9","DOIUrl":"https://doi.org/10.1007/s10787-025-01824-9","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment, depression, and a lower quality of life (QoL) are among the metabolic and neuropsychiatric consequences linked to type 2 diabetes mellitus (T2DM). The pharmacological management of T2DM often involves sodium-glucose co-transporter 2 inhibitors (SGLT2i) and sulfonylureas (SUs), both of which have been shown to influence metabolic control and inflammation. However, their differential effects on neuroinflammatory markers and neuropsychiatric outcomes remain poorly understood. This study aims to compare the effects of SGLT2i and SUs on key metabolic (mTOR, PI3K, AkT), neuroinflammatory (HMGB1, TLR4, ADAM-10, TNF-α, IL-1β, IL-6), and neuroprotective biomarkers (Klotho) associated with cognitive impairment, depression, and QoL in patients with T2DM.</p><p><strong>Methods: </strong>A case-control study was conducted with 166 participants divided into three groups: healthy controls (n = 55), SGLT2i-treated patients (n = 57), and SUs-treated patients (n = 54). The study assessed anthropometric measurements, biochemical markers, kidney function, serum neuroinflammatory and metabolic biomarkers, cognitive function (MoCA), depression (PHQ-9), and QoL (SF-36) through standard protocols.</p><p><strong>Results: </strong>Both SGLT2i and SUs significantly increased neuroinflammatory biomarkers (HMGB1, ADAM-10, TNF-α, IL-1β, IL-6) along with mTOR and Klotho compared to the healthy control group (p < 0.001). However, SGLT2i showed a more favourable reduction in these markers. Cognitive impairment and depression were more pronounced in the SUs group (MoCA: 20.03 ± 2.04, PHQ-9: 8.2 ± 1.67) compared to SGLT2i (MoCA: 22.51 ± 4.2, PHQ-9: 6.5 ± 3.8) (p < 0.001).</p><p><strong>Conclusion: </strong>SGLT2i are more effective than SUs in modulating metabolic and neuroinflammatory biomarkers and may offer better neuropsychiatric outcomes, potentially improving overall QoL in T2DM patients. Further research is needed to explore the long-term effects of these drugs on neurodegeneration and cognitive health.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin as a potential candidate for treating systemic sclerosis.","authors":"Giada Cimino, Federica Rapisarda, Rossella Talotta","doi":"10.1007/s10787-025-01820-z","DOIUrl":"https://doi.org/10.1007/s10787-025-01820-z","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a peculiar connective tissue disease characterized by a unique scenario that combines autoreactive cell activation with endothelial dysfunction and tissue fibrosis. Due to the only partially understood pathogenesis, the treatment of the disease is still controversial. Baicalin is a natural flavonoid extracted from the roots of Scutellaria baicalensis. It has been shown to be effective in preclinical models of pulmonary arterial hypertension, trophic ulcers, liver fibrosis, cancer and immune-mediated diseases. Baicalin may act via multiple mechanisms ranging from antagonizing TLR4-induced signaling to inhibiting the TGF-β/Smad3 pathway or enhancing antioxidant mechanisms. These pharmacologic properties make this agent a potential candidate for counteracting the pathogenic triad occurring in SSc. The aim of this narrative review is to summarize current knowledge on the effects of baicalin in contrasting vasculopathy, immune dysfunction and fibrosis and to explain the rationale for its use in SSc. As the efficacy/safety profile of baicalin has not been tested in SSc patients, further studies are indeed warranted.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins could improve short-term prognosis in patients with traumatic brain injury: a propensity-matched cohort study.","authors":"Ping Li, Qiang Liu, Zhuo Zhang, Hu Nie","doi":"10.1007/s10787-025-01803-0","DOIUrl":"https://doi.org/10.1007/s10787-025-01803-0","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether the use of statins could improve the short-term prognosis of traumatic brain injury (TBI) patients and explore the relationship between the initiation time and duration of post-traumatic statins treatment and short-term prognosis.</p><p><strong>Methods: </strong>TBI patients in the MIMIC IV database were divided into a statin group and a control group. A comparison was made between them in terms of short-term prognosis, including ICU mortality, in-hospital mortality, 28-day mortality, and 90-day mortality. Three subgroup analyses were conducted in this study. Propensity score matching (PSM) method was employed to balance the baseline characteristics. Further stratification based on statin treatment initiation time and duration resulted in four groups.</p><p><strong>Results: </strong>A total of 1124 eligible TBI patients were included in this study. Before PSM, there were no significant differences between the two groups in terms of the four indexes. After PSM, the statin group showed significantly lower ICU mortality, in-hospital mortality, 28-day mortality, and 90-day mortality compared to the control group. Similarly, after conducting PSM for the three subgroup analyses, similar results were obtained for the GCS < 8 and age greater than 65 years subgroups. In the subgroup analysis of the cohort aged 65 years or under, there were no significant differences in the four metrics between the two groups. The analysis found no discernible correlation between the initiation time and duration of statin treatment and TBI patient prognosis.</p><p><strong>Conclusion: </strong>Post-traumatic use of statins can improve the short-term prognosis of TBI patients. In comparison to patients aged ≤ 65 years, TBI patients aged > 65 years who use statin drugs experience significantly better short-term prognosis. The correlation between the initiation time and duration of statin treatment and the prognosis of TBI patients warrants further investigation.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hibiscus sabdariffa L. (Roselle flower) extract exerts protective effects against lipopolysaccharide-induced inflammation by ameliorating TLR4/NF-κB and NLRP3 inflammasome activation.","authors":"Narongsuk Munkong, Atcharaporn Ontawong, Natthaphon Thatsanasuwan, Sirinat Pengnet, Jiradej Makjaroen, Phorutai Pearngam, Saharat Nanthawong, Poorichaya Somparn, Natnisha Leelahavanichkul, Arthid Thim-Uam","doi":"10.1007/s10787-025-01783-1","DOIUrl":"https://doi.org/10.1007/s10787-025-01783-1","url":null,"abstract":"<p><p>The phytochemical constituents of various plant extracts have shown potential in mitigating oxidative stress and inflammation. Hibiscus sabdariffa L. (HS), known as the roselle flower, has demonstrated antioxidant and anti-inflammatory effects in several models. Our study aimed to evaluate the effects of aqueous HS extract on modulating the TLR4/MyD88/NF-κB and Caspase-11/NLRP3 inflammasome signaling pathways during lipopolysaccharide (LPS)-induced mitochondrial stress and inflammation in macrophages by several in vitro assays. The results demonstrated that compared with LPS alone, HS extract significantly reduced the production of ROS, nitric oxide and proinflammatory cytokines (IL-6, TNF-α, PG-E2, IL-1β, and IFN-γ) by lowering the gene expression of p^22phox and iNOS and suppressed IκBα-dependent NF-κB signaling. Furthermore, HS treatment induced the polarization of macrophages from the M1 phenotype to the M2 phenotype, as demonstrated by qPCR and flow cytometry. The proteomic data revealed that HS extract can downregulate the expression of several mitochondria-associated proteins and reduce mitochondrial DNA leakage during LPS activation, suppressing Caspase-11/Gasdermin-D /NLRP3 inflammasome activation. In summary, the protective effects of HS extract against LPS-induced inflammation, which is mediated through the TLR4/NF-κB/NLRP3 signaling pathway, may significantly promote anti-inflammatory responses and alleviate related diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-colitic effects of Oldenlandia umbellata L. through NF-κB pathway inhibition in a DSS-induced mouse model.","authors":"X Janet Bertilla, S Rupachandra","doi":"10.1007/s10787-025-01808-9","DOIUrl":"https://doi.org/10.1007/s10787-025-01808-9","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an inflammatory bowel disease marked by epithelial barrier dysfunction and hyperactivation of immune signaling, particularly in the NF-κB pathway. Conventional therapies are limited by side effects and relapse risk, highlighting the need for safer, plant-based interventions. Oldenlandia umbellata L., a traditional herb, has demonstrated anti-inflammatory potential but remains underexplored in gastrointestinal disorders.</p><p><strong>Objective: </strong>This study investigates the therapeutic efficacy of a methanolic extract of O.umbellata L. (MEOU) in a dextran sulfate sodium (DSS)-induced mouse model of colitis, focusing on its effects on clinical symptoms, histopathology, intestinal permeability, cytokine expression, and NF-κB signaling.</p><p><strong>Methods: </strong>Acute colitis was induced in BALB/c mice with 5% DSS for 7 days, followed by oral treatment with MEOU (100, 200 or 400 mg/kg) and prednisolone (5 mg/kg) for another 7 days. Clinical parameters (body weight, Disease Activity Index (DAI), colon and spleen morphology, and histopathology were evaluated. Intestinal permeability was measured by FITC-dextran assay, while TNF-α, IL-6 mRNA levels, and NF-κB p65 protein levels were analyzed by RT-qPCR and Western blot, respectively.</p><p><strong>Results: </strong>MEOU significantly attenuated weight loss, reduced DAI scores, and reversed colon shortening and splenomegaly in a dose-dependent manner. Histological analysis revealed preserved mucosal structure and reduced inflammatory infiltration. FITC-dextran assays confirmed improved barrier integrity. Molecular analyses showed that MEOU downregulated pro-inflammatory cytokines and suppressed NF-κB p65 activation.</p><p><strong>Conclusion: </strong>MEOU exhibits potent anti-colitic activity through anti-inflammatory and barrier-protective mechanisms by NF-κB pathway inhibition, supporting its potential as a plant-based therapeutic for UC.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring potential biomarkers and signaling pathways in neuroinflammation post-traumatic brain injury: insights for synthetic compound-based interventions.","authors":"Mohit Kumar, Jasmine Chaudhary, Akash Jain","doi":"10.1007/s10787-025-01823-w","DOIUrl":"https://doi.org/10.1007/s10787-025-01823-w","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Traumatic brain injury (TBI) is a major reason for mortality and long-term neurologic disability worldwide, primarily resulting from road accidents, falls, and sports injuries. This review focuses on the potential biomarkers and signaling pathways involved in neuroinflammation, post-traumatic brain injury and synthetic compound-based treatment approaches.</p><p><strong>Recent findings: </strong>Neuroinflammation is a critical component of TBI pathology, initiated by the activation of microglia and astrocytes, release of pro-inflammatory mediators, and permeation of peripheral immune cells. While inflammation is essential for debris clearance and tissue repair, excessive or chronic inflammation exacerbates neuronal damage, impairs neurogenesis, and hinders functional recovery. This dual role of neuroinflammation highlights the targeted therapeutic strategies to modulate the inflammatory response. Anti-inflammatory cytokines work to limit inflammation, while pro-inflammatory cytokines and small-molecule drugs reduce inflammation through glucocorticoid receptor activation. Emerging therapeutic approaches focus on attenuating pathologic inflammation while preserving its reparative functions. Pharmacologic agents, such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and experimental compounds targeting specific cytokines or signaling pathways, show promise in preclinical studies. Despite encouraging preclinical results, clinical studies have produced mixed outcomes, highlighting the need for further research. This review explores the molecular mechanisms underlying neuroinflammation in TBI, evaluates current and emerging therapeutic strategies, and discusses the challenges of translating these approaches into clinical practice. To improve prognosis for individuals with TBI and create effective treatments, it is crucial to comprehend the intricate interactions between neuroinflammation and TBI pathophysiology.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acteoside as a multifunctional natural glycoside: therapeutic potential across various diseases.","authors":"Reham A Mohammed, Ahmed S Kamel, Merhan O Hindam, Ahmed M El-Dessouki, Hend A Hamouda, Nehal M Ramadan, Sarah S Mohamed, Riham A El-Shiekh, Nada M Kamel","doi":"10.1007/s10787-025-01811-0","DOIUrl":"https://doi.org/10.1007/s10787-025-01811-0","url":null,"abstract":"<p><p>Phenylethanoid glycosides are naturally occurring water-soluble molecules with remarkable biological characteristics that are abundant throughout the plant world. Acteoside (AC) is a phenylethanoid glycoside that was first discovered in mullein, but is also found in various other plant species. It has four moieties: caffeic acid, glucose, rhamnose, and phenylethyl alcohol. AC is an important bioactive natural compound isolated from many plant species. Extracts from different plant species, including Barleria prionitis, B. lupulina, Rhinacanthus nasutus, Orthosiphon aristatus, and Nicoteba betonica, have high quantities of AC. AC is hydrophilic in nature, and it has several bioactivities such as anti-inflammatory, antibacterial, antiviral, antioxidant, antidiabetic, neuroprotective, cardioprotective, anticancer, and wound-healing properties. In this review, we discuss its prominent pharmacological properties. The findings provide valuable insights for future research on AC which exhibit promising anti-inflammatory activities.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential impact of clindamycin on neurosurgery patients: a randomized controlled trial.","authors":"Lobna W Alam El-Din, Noha A El-Bassiouny, Wael M Khedr, Rehab H Werida","doi":"10.1007/s10787-025-01810-1","DOIUrl":"https://doi.org/10.1007/s10787-025-01810-1","url":null,"abstract":"<p><strong>Purpose: </strong>The study investigates whether adding clindamycin to neurosurgery patients' as a postsurgical management regimen improves recovery, provides neuroprotection, and prevents neurological complications. Neuron-specific enolase (NSE) and neurotensin (NT) were measured as biomarkers of inflammation, brain damage, and neuronal apoptosis.</p><p><strong>Methods: </strong>Patients were randomly assigned into two groups (n = 22 each) to receive the standard management plus either ceftriaxone (2 g / 12 h) or plus ceftriaxone and clindamycin (900 mg/8 h) as a combination therapy for seven days.</p><p><strong>Results: </strong>NSE serum levels in the clindamycin and control group on day 3 were (10.01 ± 1.64) versus (23.77 ± 11.75), respectively (p = 0.0001). NT serum levels in the clindamycin and control groups on day 3 were (4.5 ± 2.8) versus (8.29 ± 7.97), respectively (p = 0.0418). Glasgow Coma Scale (GCS) on day 3 was (14.32 ± 1.13) versus (14.23 ± 1.31) in the clindamycin and the control groups, respectively, (p = 0.724). SOFA score assessed on day 3 (5 (22.7%)) and (1 (4.5%)) had grade 1, (15 (68.25)) and (14 (63.35)) had grade 2, (1 (4.5%)) and (5 (22.7%)) had grade 3, (0 (0.0%)) and (1 (4.5%)) had grade 4, and (1 (4.5%)) and (1 (4.5%)) had grade 5 in the clindamycin and control groups, respectively.</p><p><strong>Conclusion: </strong>Adjunctive use of clindamycin might be a novel option that reduces secondary neurological injury/damage after neurosurgeries. Further and more extensive clinical trials are warranted to confirm the findings.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease: exploring the systemic immune mechanisms through molecular investigations.","authors":"Maneesh Mohan, Ashi Mannan, Thakur Gurjeet Singh","doi":"10.1007/s10787-025-01816-9","DOIUrl":"https://doi.org/10.1007/s10787-025-01816-9","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder that is mainly caused by the degeneration of dopaminergic neurons of the substantia nigra. Although the pathological feature involves α-synuclein aggregation, recent findings suggest that systemic immune dysregulation is a key process in initiating and advancing the disease. This article seeks to untangle the complex molecular mechanisms that contribute to the immune response in PD, with specific emphasis on innate and adaptive immune processes. α-Synuclein-induced T-cell-mediated neuronal degeneration reveals a causal relationship between peripheral immunity and central neurodegeneration. At the same time, stimulation of innate immune sensors like the NLRP3 inflammasome in microglia has been found to accelerate neuroinflammation and lead to neuronal loss. Mitochondrial dysfunction, another key hallmark of PD, leads to defective mitophagy and release of mitochondrial danger-associated molecular patterns (DAMPs), further exaggerating inflammatory signals through NLRP3 and other mechanisms. Moreover, defective autophagic and lysosomal degradation machinery may perpetuate chronic inflammation and immune cell activation. Gut microbiota-gut-associated lymphoid tissue-peripheral immune cell interaction with the blood-brain barrier also comes into play as a key player in PD neuroimmune cross-talk. We specifically address therapeutic implications, focusing on the promise of immune checkpoint targeting, inhibition of inflammasomes, and mitophagy improvement as new disease-modifying approaches. Elucidation of these complex immune mechanisms offers key insights into PD pathophysiology and opens promising immunomodulatory therapeutic paths. This review integrates cutting-edge discoveries and outlines a shared model to improve understanding of the systemic immune setting in Parkinson's disease.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}