Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: July 30, 2024

Abstract Background Isoprostanes and prostaglandins are biomarkers for oxidative stress inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify association of isoprostanes with Amyloid, Tau, Neurodegeneration (ATN) (Aβ-42, p-tau, t-tau) AD mild cognitive impairment (MCI) subjects. Methods Targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) 147 paired plasma-CSF samples from Ace Alzheimer Center Barcelona 58 CSF MCI patients Mannheim/Heidelberg cohort. Linear regression used evaluate metabolites levels ATN overall sample stratified by Aβ-42 pathology APOE genotype. We further evaluated dementia progression. Results Increased PGF2α, 8,12-iso-iPF2α VI, 5-iPF2α VI were significantly associated (False discovery rate (FDR) < 0.05) higher p-tau levels. Additionally, increased total tau CSF. due AD, PGF2α both tau, whereases specifically analysis, t-tau observed only ε4 carriers while showed ε33 carriers. 8,12- iso-iPF2α ε33/ ε3 None evidence Conclusions Oxidative (8,12-iso-iPF2α VI) inflammatory (PGF2α) correlated during prodromal stage relation markers may be influenced

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Modified Decision Tree with Custom Splitting Logic Improves Generalization across Multiple Brains’ Proteomic Data Sets of Alzheimer’s Disease

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Many factors negatively affect a generalization of the findings in discovery proteomics. They include differentiation between patient cohorts, variety experimental conditions, etc. We presented machine-learning-based workflow for proteomics data analysis, aiming at improving generalizability across multiple sets. In particular, we customized decision tree model by introducing new parameter, min_groups_leaf, which regulates presence samples from each set inside model's leaves. Further, analyzed trend feature importance's curve as function novel parameter selection to list proteins with significantly improved generalization. The developed was tested using five proteomic sets obtained post-mortem human brain Alzheimer's disease. consisted 535 LC–MS/MS acquisition files. results were two different pipelines processing: (1) MS1-only processing based on DirectMS1 search engine and (2) standard MS/MS-based one. Using workflow, found seven expression patterns that unique asymptomatic Alzheimer patients. Two them, Serotransferrin TRFE DNA repair nuclease APEX1, may be potentially important explaining lack dementia patients neuritic plaques neurofibrillary tangles.

Language: Английский

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Anti-inflammatory and antioxidant effects of baicalein: targeting Nrf2, and NFĸB in neurodegenerative disease

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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World no-tobacco: effects of second-hand smoke (SHS) and vapors on the developing and adult brain

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 6, 2025

The goal of this review is to highlight the role second-hand smoke (SHS) or environmental tobacco (ETS) and e-cigarette (EC) vapors on brain integrity function during development adulthood, including how it relates increasing risk for age-related neurodegenerative disorders. A systematic literature effect SHS ETS revealed a total 284 372 publications 312 publications, respectively. After taking into account duplicate focused policy, surveys other organs than brain, there are limited studies effects SHS, EC structure function. In review, we examine major constituents in their health, mechanisms by which alters function, behavioral cognitive performance. We hope that will encourage investigators explore further short-as well long-term vapor exposure developing adult better understand its neurodevelopmental disorders diseases ultimately develop therapeutic modalities reduce even prevent short- detrimental health.

Language: Английский

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UPLC-ESI–MS/MS phytochemical profile, in vitro, in vivo, and in silico anti-Alzheimer’s activity assessment of Pithecellobium dulce (Roxb.) Benth. leaves

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 5, 2025

Abstract Background Alzheimer's (AD) is a neurological disorder that worsens the quality of life and raises need for caretakers with no available curative medication illness. Therefore, there growing concern about use herbal medicine, as it cost-effective, has minimal side effects, could slow AD progression enhance patients' life, making viable adjuvant therapy. Pithecellobium dulce (Roxb.) Benth F. Leguminosae widely consumed in several countries to treat various illnesses. This study used vitro, vivo, silico studies investigate potential P. leaves' methanolic extract treating preventing disease. Results The vitro showed inhibited 77% acetylcholinesterase (AChE) activity, IC 50 value was 19.23 ± 1.02 µg/ml. vivo scopolamine-induced confirmed result by significantly inhibiting AChE, dopamine, noradrenaline, malondialdehyde levels increasing acetylcholine, glutathione levels. A phytochemical analysis leaves using UPLC-ESI–MS/MS revealed 67 compounds different chemical classes, 22 flavonoids, 17 phenolic organic acids, 8 fatty 3 sterols, 6 amino acids alkaloids, 5 coumarins, 2 anthraquinones, 1 sugar, lignin, terpene, hydrocarbon. It found 5, 7, 3′, 4′, 5′-pentahydroxy-3, 6, 8-tri-methoxy flavone had strongest binding affinity AChE (− 18.8 kcal/mol). Different computational modeling methods were employed, including principal component analysis, ligand-residue interaction, dynamics cross-correlation matrices thermodynamics calculation. ACh protein decreased fluctuation influenced ligand optimum orientation on conformational space. Additionally, drug energy residue correlation flavone-AChE system increased. Conclusion contains secondary metabolites promisingly be safe effective natural treatment complications through antioxidant acetylcholinesterase, noradrenaline inhibition activities also acetylcholine level brain. Graphical abstract

Language: Английский

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Postoperative Delirium and Cognitive Dysfunction After Cardiac Surgery: The Role of Inflammation and Clinical Risk Factors

Diagnostics, Journal Year: 2025, Volume and Issue: 15(7), P. 844 - 844

Published: March 26, 2025

Background/Objectives: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are prevalent neurological complications following cardiac surgery, significantly affecting patient recovery long-term outcomes, including increased risk of persistent impairment, functional decline, mortality. Understanding the underlying mechanisms factors for POD/POCD is crucial improving perioperative management. This study aimed to investigate relationship between systemic inflammation, assessed through inflammatory markers, occurrence POD POCD in patients undergoing surgery. Methods: We prospectively enrolled 88 aged 18-79 years open-heart Patients with preoperative impairment or high surgical (based on EuroSCORE SOFA scores) were excluded focus impact inflammation a relatively unselected cohort. responses (CRP, NLR, IL-6, IL-17A, SII, SIRI) measured, (CAM-ICU) (neuropsychological testing) during hospitalization at 3 months follow-up. Statistical comparisons performed who developed those did not. Results: was confirmed across cohort, significant increases CRP, SIRI. While correlational analyses changes individual markers not statistically entire exhibited higher levels IL-6 NLR 48 h postoperatively (p < 0.05). Established clinical associated included older age, prolonged cardiopulmonary bypass (CPB) duration, extended mechanical ventilation, vasopressor support blood transfusion, renal dysfunction, elevated creatine kinase (CK) lactate dehydrogenase (LDH) Ejection fraction (EF) 45% atrial fibrillation (AF) also more group. Conclusions: Our findings emphasize role response, particularly conjunction established factors, development after levels, readily measurable cost-effective may contribute identifying risk. Comprehensive management strategies targeting modifiable organ function mitigating outcomes this vulnerable population.

Language: Английский

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Radiofrequency radiation and Alzheimer’s disease: harmful and therapeutic implications

International Journal of Radiation Biology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: March 25, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and cognitive decline. The relationship between AD radiofrequency (RF) radiation emitted wireless devices remains under investigation. aim of this review to comprehensively explore the effects RF on evaluating existing literature. This used Web Science, Scopus, PubMed find relevant studies radiation. evaluates total 81 studies, including animal models, human in vitro experiments, with results summarized tables for clarity. Some suggest aggravates increasing oxidative stress, impairing blood-brain barrier integrity, promoting amyloid-beta deposition. Conversely, other indicate may have protective benefits, such as enhancing brain mitochondrial functions reducing levels. Understanding RF-AD relationship, parameters like frequency exposure time, crucial therapeutic strategies. reviewed highlight radiation's dual AD, underscoring need detailed approach. Further are required clarify these inform preventive measures.

Language: Английский

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3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one Attenuates Scopolamine-induced Cognitive Impairment in Rats: Insights Into Neuroprotective Effects

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Language: Английский

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Protective effect of Spondias mombin leaf extracts against aluminum chloride-induced brain oxidative stress, inflammation and apoptosis in rats

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 23, 2025

Abstract Background Aluminum is recognized for its toxicity in humans and animals. This study investigates the protective effects of Spondias mombin leaf extracts against oxidative stress, inflammation, apoptosis male Wistar rats. Rats were divided into nine groups, receiving 100 mg/kg AlCl 3 weeks, followed by a 2-week treatment with extract (SME) or fraction (SMF) at 200 mg/kg. Brain tissues analyzed using biochemical, molecular, histopathological techniques. Results Phytochemical analysis confirmed presence tannins, phenols, terpenoids, flavonoids steroids, while HPLC identified kaempferol other polyphenols, extracts. exposure led to increased inflammatory damage brain tissue as revealed decreased glutathione concentrations antioxidant enzyme activities, along elevated levels tumor necrosis factor-alpha, nitric oxide, myeloperoxidase, xanthine oxidase, lactate dehydrogenase. Caspase-3, BCL2 associated X (Bax) also -exposed Both SME SMF mitigated -induced redox imbalance, proinflammatory events, neuronal cell death enhancing reduced reducing biomarkers, preserving hippocampal formation organization. Conclusions These findings highlight therapeutic potential aluminum-induced neurotoxic through their antioxidant, anti-inflammatory, antiapoptotic properties. Graphical abstract

Language: Английский

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