Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health

Current Pharmaceutical Design, Год журнала: 2024, Номер 30(5), С. 323 - 332

Опубликована: Фев. 1, 2024

Abstract: Neuroinflammation represents a critical immune response within the brain, playing pivotal role in defense against injury and infection. However, when this becomes chronic, it can contribute to development of various neurodegenerative psychiatric disorders. This bibliographic review delves into vitamin D modulating neuroinflammation its implications for brain health, particularly context neurological While is traditionally associated with calcium homeostasis bone also exerts immunomodulatory neuroprotective effects central nervous system. Through comprehensive analysis preclinical clinical studies, we uncover how D, acting through receptors glial cells, may influence production proinflammatory cytokines antioxidants, potentially mitigating cascade events leading neuronal damage. Clinical research has identified deficiency as common thread increased risks multiple sclerosis, Parkinson's disease, Alzheimer's, depression, among others. Furthermore, models suggest D's regulatory capacity over inflammatory mediators, protective apoptosis, contribution neurogenesis synaptic plasticity. These insights underscore potential supplementation not only slowing progression diseases but improving quality life patients suffering from conditions. Future studies are essential validate these findings further our understanding prevent or alleviate symptoms, opening new avenues therapeutic strategies neuroinflammation-related pathologies. crucial injuries infections, persistence lead such Parkinson's, depression. Cholecalciferol (Vitamin D3) emerges regulator neuroinflammation, present cells astrocytes microglia, function. Vitamin mechanisms action include cytokine modulation regulation nuclear mitochondrial genes. It adjusts mediators resulting effects. Additionally, impacts neurotransmitter synthesis positions adjunct treating like Alzheimer's Parkinson's. Lastly, intestinal microbiota serotonin contributes disorders schizophrenia Thus, presents novel approach neuroinflammatory, neurodegenerative, neuropsychiatric diseases.

Язык: Английский

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CPT1A ameliorates microglia-induced neuroinflammation via facilitating VDR succinylation

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 12, 2025

Neurodegenerative diseases, characterized by impairments in cognition, memory, and movement, are becoming increasingly prevalent due to population aging, posing a significant threat public health. Extensive evidence suggests that neuroinflammation, mediated microglia, plays crucial role the development of these diseases. Notably, vitamin D receptor (VDR) has been shown regulate microglia activation controlling function neuroprotective D. This study aims elucidate potential VDR modulating neuroinflammation. To mimic BV2 cells were treated with lipopolysaccharide (LPS) for 12 h. Enzyme-linked immunosorbent assays (ELISAs) used measure release cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, MCP-1, TNF-α. Western blot performed assess relative protein expressions succinylation modifications. Co-immunoprecipitation (Co-IP) experiments conducted determine interaction between carnitine palmitoyltransferase 1A (CPT1A). Immunofluorescence staining was analyze localization VDR, CPT1A, COX-2, CD11b. Our findings demonstrated expression upregulated exposed LPS. Ectopic attenuated inflammatory response activation. We discovered (CPT1A) promoted succinylation. Further investigations revealed CPT1A enhanced stability binding lysine K117 being primary site. Importantly, depletion abrogated protective effects overexpression on microglia-mediated highlighted functioned as suppressor neuroinflammation facilitating succinylation, offering therapeutic targets management neurodegenerative

Язык: Английский

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Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders

Molecular Neurobiology, Год журнала: 2024, Номер 61(9), С. 7211 - 7238

Опубликована: Фев. 19, 2024

Язык: Английский

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Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies

Journal of Alzheimer s Disease, Год журнала: 2024, Номер 98(2), С. 373 - 385

Опубликована: Март 5, 2024

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent excess dementia conferred by is less clear. Objective: We summarized current from several aspects further quantified these associations. Methods: collected relevant prospective cohort studies searching PubMed, Embase Cochrane up to July 2023. The pooled relative risks (RR) were evaluated random-effects models. Dose-response analyses conducted method two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 eligible for inclusion in meta-analyses, among which 9 4 literatures included dose-response Alzheimer’s disease (AD). Vitamin exhibited a 1.42 times (95% confidence interval (CI) = 1.21–1.65) 1.57-fold AD CI 1.15–2.14). And was associated with 34% elevated 1.19–1.52). Additionally, non-linearly related (pnonlinearity 0.0000) 0.0042). approximate 77.5–100 nmol/L 25-hydroxyvitamin [25(OH)D] optimal reducing risk. seemed be decreased when 25(OH)D level >40.1 nmol/L. Conclusions: factor dementia, AD, impairment. nonlinear relationships may provide optimum dose prevention.

Язык: Английский

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Role of Calcitriol and Vitamin D Receptor (VDR) Gene Polymorphisms in Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4806 - 4806

Опубликована: Апрель 28, 2024

Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) the active form D, generated kidney many other tissues/organs, including brain. It a steroid hormone that regulates important functions like calcium/phosphorous levels, bone mineralization, immunomodulation, indicating its broader systemic significance. In addition, calcitriol confers neuroprotection mitigating oxidative stress neuroinflammation, promoting clearance Aβ, myelin formation, neurogenesis, neurotransmission, autophagy. The receptors to which binds (vitamin receptors; VDRs) exert effects are distributed over organs tissues, representing significant roles beyond sustaining health. biological manifested through genomic (classical) non-genomic actions different pathways. first slow effect involving nuclear VDR directly affecting gene transcription. with polymorphisms relies on changes consumption, lowers expression, protein stability, binding affinity. leads altered expression genes involved neuroprotective calcitriol. This review summarizes mechanism role AD, might help develop potential therapeutic strategies markers for future.

Язык: Английский

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Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

European Journal of Neuroscience, Год журнала: 2024, Номер 60(1), С. 3466 - 3490

Опубликована: Май 10, 2024

Abstract In females, Alzheimer's disease (AD) incidences increases as compared to males due estrogen deficiency after menopause. Estrogen therapy is the mainstay for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. plays crucial role amyloid precursor protein (APP) processing overall neuronal health by regulating various factors such brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes apolipoprotein E (ApoE) polymorphisms. All these impact physiology of postmenopausal women. replacement therapies play an important treatment strategy prevent However, use may lead increased risks breast cancer, venous thromboembolism cardiovascular disease. Various therapeutic approaches have used mitigate effects on AD. These include therapy, Selective Receptor Modulators (SERMs), Beta (ERβ)‐Selective Agonists, Transdermal Delivery, Localised Combination Therapies, Metabolism Modulation Alternative Estrogenic Compounds like genistein from soy, notable phytoestrogen plant sources. mechanism via which modulate women not explained earlier thoroughly. Present review will enlighten all molecular mechanisms Along‐with this, association between estrogen, ApoE polymorphisms also be discussed

Язык: Английский

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Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction

Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102087 - 102087

Опубликована: Окт. 11, 2023

Язык: Английский

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Modulation of the vitamin D/vitamin D receptor system in osteoporosis pathogenesis: insights and therapeutic approaches

Journal of Orthopaedic Surgery and Research, Год журнала: 2023, Номер 18(1)

Опубликована: Ноя. 13, 2023

Abstract Osteoporosis is a prevalent bone disorder characterized by low mineral density (BMD) and deteriorated microarchitecture, leading to an increased risk of fractures. Vitamin D (VD), essential nutrient for skeletal health, plays vital role in maintaining homeostasis. The biological effects VD are primarily mediated through the vitamin receptor (VDR), nuclear that regulates transcription target genes involved calcium phosphate metabolism, mineralization, remodeling. In this review article, we conduct thorough literature search PubMed EMBASE databases, spanning from January 2000 September 2023. Utilizing keywords “vitamin D,” receptor,” “osteoporosis,” “therapy,” aim provide exhaustive overview VD/VDR system osteoporosis pathogenesis, highlighting most recent findings field. We explore molecular mechanisms underlying VDR’s on cells, including osteoblasts osteoclasts, discuss impact VDR polymorphisms BMD fracture risk. Additionally, examine interplay between other factors, such as hormonal regulation, genetic variants, epigenetic modifications, contribute susceptibility. therapeutic implications targeting pathway management also discussed. By bringing together these diverse aspects, enhances our understanding system’s critical pathogenesis highlights its significance potential target.

Язык: Английский

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Follow-Up Period Affects the Association between Serum 25-Hydroxyvitamin D Concentration and Incidence of Dementia, Alzheimer’s Disease, and Cognitive Impairment

Опубликована: Авг. 14, 2024

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard or odds ratios) are determined for incidence participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below above specified values. Serum 25(OH)D vary over time, thereby diluting the of long follow-up periods. Inverse relationships between RR and period have been reported all-cause mortality rate cancer rates. Here I evaluate neurological outcomes. Methods: analyzed how affected results from 10 studies dementia, 6 Alzheimer’s disease, 9 cognitive impairment respect to vitamin deficiency. Results: For impairment, respectively, linear regression fits = 2.9 – 0.14 × years, r 0.73, p 0.02; 0.69, 0.13; 1.8 0.066 0.72, 0.03. The fit shortest each outcome considered best estimate deficiency’s risk. Those values approximately twice that found by averaging all RRs without considering period. Conclusions: conditions should be relatively short periods after repeated measurements as warranted during follow-up.

Язык: Английский

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Vitamin D receptor FokI polymorphism as a risk factor for painful diabetic neuropathy in type 2 diabetes mellitus patients

Journal of Neurogenetics, Год журнала: 2025, Номер unknown, С. 1 - 9

Опубликована: Март 12, 2025

Painful diabetic neuropathy (PDN) is a common complication in patients with type 2 diabetes mellitus (T2DM) disruption of vitamin D (VD) activity as one the risk factors. Active VD exerts its biological functions through receptor (VDR), which polymorphisms VDR gene can impair. This study aims to establish FokI and ApaI factors for PDN. case-control used samples from T2DM without Neuropathic pain was diagnosed using DN4 questionnaire, while were examined Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. Other included gender, hypertension, current insulin use, obesity, HbA1c levels, dyslipidemia. A total 64 subjects involved study. The polymorphism (CT+TT genotype) significant factor PDN (OR 4.20; 95% CI [1.47-11.94]; p = 0.012). T allele significantly increased by 2.8 times 2.78; [1.28-6.01], 0.014). not associated Diabetes duration ≥4.5 years uncontrolled other Multivariate analysis identified three variables: 5.00; [1.37-18.24], 0.015), use 4.95; [1.37-17.87], 3.47; [1.03-11.69], 0.045). genetic patients.

Язык: Английский

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