Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review

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

Published: Jan. 24, 2025

Polyphenols, naturally occurring phytonutrients found in plant-based foods, have attracted significant attention for their potential therapeutic effects neurological diseases and neuroinflammation. These compounds possess diverse neuroprotective capabilities, including antioxidant, anti-inflammatory, anti-amyloid properties, which contribute to mitigating the progression of neurodegenerative conditions such as Alzheimer's Disease (AD), Parkinson's (PD), Dementia, Multiple Sclerosis (MS), Stroke, Huntington's (HD). Polyphenols been extensively studied ability regulate inflammatory responses by modulating activity pro-inflammatory genes influencing signal transduction pathways, thereby reducing neuroinflammation neuronal death. Additionally, polyphenols shown promise various cellular signaling pathways associated with viability, synaptic plasticity, cognitive function. Epidemiological clinical studies highlight polyphenol-rich diets decrease risk alleviate symptoms disorders Furthermore, demonstrated through regulation key Akt, Nrf2, STAT, MAPK, play critical roles neuroprotection body's immune response. This review emphasizes growing body evidence supporting combating neurodegeneration neuroinflammation, well enhancing brain health. Despite substantial promising hypotheses, further research investigations are necessary fully understand role establish them advanced targets age-related neuroinflammatory conditions.

Language: Английский

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Human and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

Murine models of Alzheimer's disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse amyloidosis. We identified shared pathways by integrating with human metadata prioritized components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% protein alterations; additional genetic incorporation tau splicing pathologies increases this similarity to 42%. dissected proteome-transcriptome inconsistency 5xFAD brains, revealing that inconsistent proteins enriched within amyloid plaque microenvironment (amyloidome). Our analysis turnover demonstrates formation delays degradation amyloidome components, including Aβ-binding autophagy/lysosomal proteins. proteomic strategy defines pathways, identifies potential targets, underscores contributes discrepancies during progression. This study maps changes models, identifying humans, amyloid-driven turnover, differences, offering insights into targets.

Language: Английский

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Porous Materials for Early Diagnosis of Neurodegenerative Diseases

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract Neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease, present formidable challenges in modern medicine due to their complex pathologies the absence of curative treatments. Despite advances symptomatic management, early diagnosis remains essential for mitigating progression improving patient outcomes. Traditional diagnostic methods, such as MRI, PET, cerebrospinal fluid biomarker analysis, are often inadequate detection these diseases. Emerging porous materials, including metal–organic frameworks (MOFs), covalent–organic (COFs), MXene, zeolites, silicon, offer promising new approaches neurodegenerative These characterized by highly tunable physicochemical properties, have potential capture concentrate disease‐specific biomarkers amyloid‐beta (Aβ), tau protein, alpha‐synuclein (α‐Syn). The integration materials into advanced biosensors real‐time holds promise revolutionizing neurodiagnostic, enabling non‐invasive, sensitive, specific platforms. Furthermore, incorporation artificial intelligence (AI) machine learning (ML) techniques analysis sensor data enhances accuracy allows more efficient interpretation profiles. AI ML can optimize feature selection, improve pattern recognition, facilitate prediction progression, making them indispensable tools personalized medicine. This review explores diagnostics, emphasizing design, functionality, synergistic role advancing clinical applications.

Language: Английский

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CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 206, P. 106826 - 106826

Published: Feb. 1, 2025

Language: Английский

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Vascular models of Alzheimer's disease: An overview of recent in vitro models of the blood-brain barrier

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106864 - 106864

Published: March 1, 2025

Language: Английский

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Retinal dysfunction in APOE4 knock‐in mouse model of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract INTRODUCTION Late‐onset Alzheimer's Disease (LOAD) is the predominant form of disease (AD), and apolipoprotein E ( APOE ) ε4 a strong genetic risk factor for LOAD. As an integral part central nervous system, retina displays variety abnormalities in Our study focused on age‐dependent retinal impairments humanized APOE4 ‐knock‐in (KI) APOE3 ‐KI mice developed by Model Organism Development Evaluation Late‐Onset (MODEL‐AD) consortium. METHODS All experiments were performed 52‐ to 57‐week‐old mice. The was assessed optical coherence tomography, fundoscopy, fluorescein angiography, electroretinography, optomotor response, gliosis, neuroinflammation. mRNA sequencing find molecular pathways. RESULTS showed impaired structure, vasculature, function, vision, increased gliosis neuroinflammation, downregulation synaptogenesis. DISCUSSION allele associated with susceptibility degeneration compared ε3 allele. Highlights Apolipoprotein (APOE) 4 exhibit structural functional deficits retina. defects are attributed show unique transcriptome, yet key brain similarities. offers non‐invasive biomarker detection monitoring disease.

Language: Английский

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An Overview of Transgenic Mouse Models for the Study of Alzheimer’s Disease

Journal of dementia and Alzheimer's disease, Journal Year: 2025, Volume and Issue: 2(1), P. 2 - 2

Published: Jan. 10, 2025

Alzheimer’s disease (AD) is the most common cause of dementia, and no cure currently available. The β-amyloid cascade AD neurofibrillary tangles are basis current understanding pathogenesis, driving drug investigation other discoveries. Up until now, models have entirely validated hypothesis. must be capable recapitulating critical events this pathology, including plaques tangles. development probably derived from amyloid precursor protein (APP) presenilin 1 (PS1) familial (FAD) mutations, while tangle-like pathology determined by tau mutations. Transgenic mouse struggle to replicate entire spectrum AD, particularly neuronal death stemming pathologies. Furthermore, success these transgenic mice often relies on overexpression APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome composition between human may hinder accurate recapitulation pathological models. Although none fully mirrors experimental vivo animal provided valuable insights into toxicity overall pathophysiological AD. Therefore, been widely used preclinical evaluation therapeutic strategies played a pivotal role immunotherapies for In review, we sum up main research, whether they mutation-based mice, plus or mice. specific characteristics each model significance their use focusing advantages disadvantages, as well progress made forthcoming challenges replicating neurodegenerative disease, also highlighted.

Language: Английский

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Evolution of Alzheimer’s Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 128 - 128

Published: Jan. 17, 2025

Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among elderly and profoundly impairing their quality life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, memantine, offer only modest symptomatic relief are frequently associated with significant adverse effects. Faced this challenge in line advances understanding pathophysiology neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge underlying pathophysiological mechanisms disease. Among alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target eliminate toxic proteins implicated AD. Additionally, use medicinal plants is examined, synergistic effects components may confer neuroprotective properties. The modulation gut microbiota also addressed a peripheral strategy that could influence neuroinflammatory degenerative processes brain. Furthermore, potential emerging approaches, microRNAs regulate key cellular nanotherapy, which enables precise drug delivery central nervous system, analyzed. Despite promising these strategies, incidence continues rise. Therefore, it proposed achieving effective treatment future require integration combined maximizing different interventions.

Language: Английский

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Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer’s risk population: A retrospective analysis

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314097 - e0314097

Published: Jan. 24, 2025

Translational validity of mouse models Alzheimer’s disease (AD) is variable. Because change in weight a well-documented precursor AD, we investigated whether diversity human AD risk phenotypes was evident longitudinally characterized cohort 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months age which equivalent 81 years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, genotype employed identify emergent trajectories phenotypes. In the hAPOE-AD cohort, five distinct emerged: three were associated with loss phenotype (36% n = 426), one gain (13% 152), trajectory no (34% 403). The AHMM model findings validated post-hoc survival analyses, revealing differences rates across identified Further validation performed using body composition plasma β-amyloid data from mice within gain, stable trajectories. Weight elevated levels, higher fat composition, lower greater proportion APOE4/4 carriers. contrast, hAPOE3/4 carriers, better predominantly male. association between observed humans mirrored model. APOE3/3 equally distributed stability. Surprisingly, despite genetic uniformity, comparable housing, diet handling, divergence points emerged for subpopulations. These are consistent heterogeneity population during aging highlight importance longitudinal phenotypic characterization advance translational preclinical models.

Language: Английский

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The ABC transporter A7 modulates neuroinflammation via NLRP3 inflammasome in Alzheimer’s disease mice

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 27, 2025

Abstract Background Specific genetic variants in the ATP-binding cassette transporter A7 locus ( ABCA7 ) are associated with an increased risk of Alzheimer’s disease (AD). transports lipids from/across cell membranes, regulates Aβ peptide processing and clearance, modulates microglial T-cell functions to maintain immune homeostasis brain. During AD pathogenesis, neuroinflammation is one key mechanisms involved. Therefore, we wanted investigate specific role activation via NLRP3 inflammasome. Methods We developed first humanized, Cre-inducible flx knock-in mouse model, crossbred it APPPS1-21 β-amyloidosis generated constitutive ko microglia Cx3cr1 -specific conditional mice. The was analyzed using histological, biochemical, molecular mass spectrometry methods. Results Constitutive knockout Abca7 gene APPPS1 mice levels Aβ42 number IBA1+ (microglia) GFAP+ (astrocytes) cells. Changes astrocytes inflammasome proinflammatory cytokines, such as IL1β TNFα. Interestingly, microglia-specific restored 42 IBA1 + GFAP NLRP3-related expression original levels. In primary glial cultures APPPS1-hA7 from newborn pups, observed that conditioned media LPS-stimulated able induce cytokine release astrocytes. Conclusions Our data suggest transporters regulate communication between through cytokines. This regulation implicates a driver ultimately involved persistence inflammatory response AD.

Language: Английский

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