New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation

Journal of Neuroimmune Pharmacology, Год журнала: 2024, Номер 19(1)

Опубликована: Фев. 29, 2024

Abstract Inflammasomes are important modulators of inflammation. Dysregulation inflammasomes can enhance vulnerability to conditions such as neurodegenerative diseases, autoinflammatory and metabolic disorders. Among various inflammasomes, Nucleotide-binding oligomerization domain leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) is the best-characterized inflammasome related inflammatory diseases. NLRP3 an intracellular sensor that recognizes pathogen-associated molecular patterns damage-associated resulting in assembly activation inflammasome. The includes NLRP3, adaptor apoptosis-associated speck-like (ASC), effector cysteine protease procaspase-1 plays imperative role caspase-1 stimulation which further initiates a secondary response. Regulation ameliorates NLRP3-mediated Much effort has been invested studying activation, exploration specific inhibitors epigenetic mechanisms controlling This review gives overview established assembly, its brief mechanistic activations well current update on non-specific could be used We also focused recently discovered mediated by DNA methylation, histone alterations, microRNAs regulating expression inflammasome, resulted novel method gaining insight into modulate activity introducing potential therapeutic strategies for CNS Graphical "Image missing"

Язык: Английский

---

Neuroprotective and anti‐inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies

Phytotherapy Research, Год журнала: 2024, Номер 38(6), С. 3169 - 3189

Опубликована: Апрель 14, 2024

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid‐beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, polyphenolic compound derived from Curcuma longa , has shown potential neuroprotective effects due its anti‐inflammatory antioxidant properties. This review aims synthesize current preclinical data on anti‐neuroinflammatory mechanisms curcumin in context AD, addressing pharmacokinetics, bioavailability, as therapeutic adjunct. An exhaustive literature search was conducted, focusing recent studies within last 10 years related curcumin's impact neuroinflammation role AD. The methodology included sourcing articles specialized databases using specific medical subject headings terms ensure precision relevance. Curcumin demonstrates significant properties modulating neuroinflammatory pathways, scavenging reactive oxygen species, inhibiting production pro‐inflammatory cytokines. Despite potential, challenges remain regarding limited bioavailability scarcity comprehensive human clinical trials. emerges promising adjunct AD multimodal benefits. However, further research required overcome establish effective dosing regimens subjects. Developing novel delivery systems formulations may enhance treatment.

Язык: Английский

---

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 104 - 104

Опубликована: Янв. 15, 2025

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of wide range brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) cause neuroinflammation, alter function, accelerate disease development. Despite progress understanding these pathways, effective medicines targeting are still limited. Traditional anti-inflammatory immunomodulatory drugs peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to central nervous system (CNS), blood-brain barrier (BBB) unwanted systemic effects. This review highlights developing treatment techniques modifying cytokine-driven focusing on advances that selectively target critical involved pathology. Novel approaches, cytokine-specific inhibitors, antibody-based therapeutics, gene- RNA-based interventions, sophisticated drug delivery systems like nanoparticles, show promise with respect lowering neuroinflammation greater specificity safety. Furthermore, developments biomarker discoveries neuroimaging improving our ability monitor responses, allowing more accurate personalized regimens. Preclinical clinical trial data demonstrate therapeutic potential tailored techniques. However, significant challenges remain, across BBB reducing off-target As research advances, creation personalized, cytokine-centered therapeutics has therapy landscape illnesses, giving patients hope better results higher quality life.

Язык: Английский

---

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

Neurorehabilitation and neural repair, Год журнала: 2023, Номер 38(1), С. 7 - 18

Опубликована: Окт. 14, 2023

Rationale: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one the highest research priorities. Methods: We convened an interdisciplinary, international group clinical pre-clinical researchers lived experience experts. identified four priority areas: (1) best measurement tools for research, (2) identification potentially modifiable causes, (3) promising interventions recommendations future trials, (4) possible biological mechanisms fatigue. Cross-cutting themes were aphasia voice experience. Working parties formed structured consensus building processes followed. Results: present 20 covering outcome measures development, testing new areas on biology post-stroke developed recommend use Clinical Assessment Tool. Conclusions: By synthesizing current knowledge in across fields, our work provides a roadmap into

Язык: Английский

---

Astroglia’s role in synchronized spontaneous neuronal activity: from physiology to pathology

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 19, 2025

The nervous system relies on a balance of excitatory and inhibitory signals. Aberrant neuronal hyperactivity is pathological phenotype associated with several neurological disorders, its most severe effects observed in epilepsy patients. This review explores the literature spontaneous synchronized activity, physiological role, aberrant forms disease. Emphasizing importance targeting underlying disease mechanisms beyond traditional neuron-focused therapies, delves into role astroglia progression. We detail how transitions from normal to state, leading epileptogenic seizures cognitive decline. Astroglia activity correlated epileptiform both animal models human tissue, indicating their potential seizure induction modulation. Understanding astroglia's dual beneficial detrimental roles could lead novel treatments for other disorders as substrate.

Язык: Английский

---

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

International Journal of Stroke, Год журнала: 2023, Номер 19(2), С. 133 - 144

Опубликована: Июль 10, 2023

Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one the highest research priorities.

Язык: Английский

---

The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury

Molecular Neurobiology, Год журнала: 2024, Номер 62(4), С. 4576 - 4590

Опубликована: Окт. 28, 2024

Язык: Английский

---

Physical exercise regulates microglia in health and disease

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Июнь 7, 2024

There is a well-established link between physical activity and brain health. As such, the effectiveness of exercise as therapeutic strategy has been explored in variety neurological contexts. To determine extent to which could be most beneficial under different circumstances, studies are needed uncover underlying mechanisms behind benefits activity. Interest grown understanding how can regulate microglia, resident immune cells central nervous system. Microglia key mediators neuroinflammatory processes play role maintaining homeostasis healthy pathological settings. Here, we explore evidence suggesting that potential microglia various animal models. We emphasize areas where future research contribute uncovering engaging exercise.

Язык: Английский

---

Effect of Modifiable Lifestyle Factors on Biological Aging

Journal of Aging Research and Lifestyle, Год журнала: 2024, Номер 13, С. 88 - 92

Опубликована: Янв. 1, 2024

Biological age is a concept that uses bio-physiological parameters to account for individual heterogeneity in the biological processes driving aging and aims enhance prediction of age-related clinical conditions compared chronological age. Although engaging healthy lifestyle behaviors has been linked lower mortality risk reduced incidence chronic diseases, it remains unclear what extent these health benefits result from slowing pace process. This short review summarized how modifiable factors - including diet, physical activity, smoking, alcohol consumption, aggregate multiple were associated with established estimates based on or cellular/molecular markers, Klemera-Doubal Method age, homeostatic dysregulation, phenotypic DNA methylation telomere length. In brief, available studies tend show consistent association physiological measures while findings regarding molecular-based metrics vary. The limited evidence highlights need further research this field, particularly life-course approach.

Язык: Английский

---

Mediterranean Diet Modulation of Neuroinflammation-Related Genes in Elderly Adults at High Cardiovascular Risk

Nutrients, Год журнала: 2024, Номер 16(18), С. 3147 - 3147

Опубликована: Сен. 18, 2024

Individuals with dementia and neurodegenerative diseases (NDDs) often suffer from cardiovascular (CVDs). Neuroinflammation driven by conditions involved in CVDs is linked to disruptions the central nervous system triggering immune reactions, perpetuating an “inflammatory-like” environment. The Mediterranean diet (MedDiet), known for its anti-inflammatory antioxidant properties, has been proposed as a key factor attenuate these risks. Blood nuclear cell samples were collected 134 participants of PREDIMED trial, which randomized three diets: one supplemented extra-virgin olive oil (MedDiet-EVOO), another nuts (MedDiet-Nuts), low-fat control diet. These analyzed at baseline 12-month follow-up assess impact dietary interventions on gene expression markers. We first selected target genes analyzing intersections between NDD CVD associations. Significant changes 12 months observed allocated MedDiet-EVOO, particularly CDKN2A, IFNG, NLRP3, PIK3CB, TGFB2. Additionally, TGFB2 changed over time MedDiet-Nuts group. Comparative analyses showed significant differences MedDiet-EVOO control, NAMPT control. Longitudinal models adjusted different covariates also revealed effects NAMPT. In conclusion, our results suggest that year traditional MedDiet, especially modulates associated risk NDDs older adults high CV risk.

Язык: Английский

---