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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The role of microglia in early neurodevelopment and the effects of maternal immune activation

Seminars in Immunopathology, Journal Year: 2024, Volume and Issue: 46(1-2)

Published: July 1, 2024

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in offspring, particularly schizophrenia and autism spectrum disorder. Microglia, tissue-resident macrophages central nervous system, are implicated as potential mediators this risk. Early development, microglia start populating embryonic addition to their traditional role responders under homeostatic conditions, also intricately involved various early processes. The timing activation may interfere functioning neurodevelopment, potentially leading long-term consequences postnatal life. In review we will discuss involvement brain development prenatal stages life, while examining effects on Additionally, recent single cell RNA-sequencing studies focusing hypothesize how life microglial priming, through epigenetic reprogramming, be related disorders.

Language: Английский

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Exploring the link between dystrophic microglia and the spread of Alzheimer's neuropathology

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Abstract Genetics and other data modalities indicate that microglia play a critical role in Alzheimer's disease progression, but details of the disease-driving influence are poorly understood. Microglial cells can be parsed into subtypes based on their histological appearance. One subtype microglia, termed dystrophic is characterized structurally by fragmented processes cytoplasmic decay, presence has been associated with ageing neurodegeneration. Recent studies suggest interaction between tau proteins amyloid-β might induce changes potentially linking pathologies to effects these microglia. We developed study human brains test hypothesis involved progression. speculated if unique neuropathological change, they would substantially more common change than neurodegenerative diseases proteinopathies, e.g. α-synuclein or transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology. Our analyses used histologically stained sections from five brain regions 64 individuals across six states, healthy controls advanced stages, including comparative conditions such as Lewy body limbic-predominant age-related TDP-43 encephalopathy change. Using stereological sampling digital pathology, we assessed populations ramified, hypertrophic found significant increase areas affected early suggesting disease-specific neuropathology. Mediation analysis structural equation modelling impact regional spread In mediation model, was initiating factor leading development which then tau. These results loss protective could contribute further research preserving microglial function warranted.

Language: Английский

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Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications

EBioMedicine, Journal Year: 2024, Volume and Issue: 111, P. 105502 - 105502

Published: Dec. 10, 2024

Language: Английский

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ADAMTS18 deficiency leads to abnormal brain methylation metabolism, dysregulated neuroinflammatory response, and unsound blood-brain barrier structure in mice

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(4)

Published: April 14, 2025

Language: Английский

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Type I interferon signalling and interferon‐responsive microglia in health and disease

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

Published: April 29, 2025

Recent evidence suggests that type I interferon (IFN‐I) signalling extends beyond its canonical roles in antiviral defence and immunomodulation. Over the past decade, dysregulated IFN‐I has been linked to genetic disorders neurodegenerative diseases, where it may contribute neurological impairments. Microglia have emerged as key mediators of responses central nervous system. A distinct transcriptional state responsive interferons recently identified microglia. The activation pathway these cells is now recognised pivotal both development neurodegeneration. This review divided into two main sections: first examines broader role system, particularly contribution dysfunction; second focuses on specific interferon‐responsive microglia, exploring mechanisms relevance conditions. Finally, we discuss how areas intersect their implications for healthy diseased states.

Language: Английский

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Unraveling microglial spatial organization in the developing human brain with DeepCellMap, a deep learning approach coupled with spatial statistics

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

Published: Feb. 13, 2025

Language: Английский

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Rethinking Depression—Beyond Neurotransmitters: An Integrated Psychoneuroendocrineimmunology Framework for Depression’s Pathophysiology and Tailored Treatment

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2759 - 2759

Published: March 19, 2025

It is known that the effectiveness of drug treatment for depression, ammine deficit based, largely unsatisfactory. In this review, we examine proposal a precision therapy has emerged and received strong push by identification role inflammation in depression. However, psychiatry risks being caught reductionist trap searching molecular switch resets whole system switches off disease. This an illusion since human complex depression systemic variable disorder. study, show inadequacy paradigm, and, at same time, illustrate superiority paradigm centered on psychoneuroendocrineimmunology (PNEI). According to PNEI disease being, caused different sources working together: psychological, biological, behavioral. means knowing biological psychological history subject, identifying relational crisis factors, building personalized treatments targeting those factors with tools medicine psychology, which are not reducible combination drugs psychotherapy. Our presents shift both theoretical practical, enables clinicians assess patients experiencing unified way treat them integrated manner.

Language: Английский

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TGF-β Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2468 - 2468

Published: Oct. 28, 2024

Microglia, the resident immune cells of central nervous system (CNS), are crucial for normal brain development and function. They become reactive in response to injury disease, a process known as microglial reactivity. This reactivity, along with homeostasis, is tightly regulated by local microenvironment interactions surrounding cells. The TGF-β signaling pathway plays an essential role this regulation. Recent genetic studies employing microglia-specific manipulation have shed light on its significance development, homeostasis review provides updated overview how modulates function contributing our understanding biology health disease.

Language: Английский

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Netrin-1 is an Important Mediator in Microglia Migration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7079 - 7079

Published: June 27, 2024

Microglia migrate to the cerebral cortex during early embryonic stages. However, precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating motility of diverse cells. In this paper, we found that promoted microglial BV2 cell vitro. Mechanism studies indicated activation GSK3β activity contributed Netrin-1–mediated migration. Furthermore, Integrin α6/β1 might be relevant receptor. Single-cell data analysis revealed higher expression α6 subunit and β1 comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, Dscam. Microscale thermophoresis (MST) measurement confirmed high binding affinity between Netrin-1. Importantly, IKVAV peptides mirrored GSK3 induced by Finally, conditional knockout (CKO) radial glial cells their progeny led a reduction population at developmental Together, our findings highlight role underscore its therapeutic potential microglia-related brain diseases.

Language: Английский

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