Pharmacology & Therapeutics, Год журнала: 2023, Номер 252, С. 108561 - 108561
Опубликована: Ноя. 10, 2023
Язык: Английский
Translational Psychiatry, Год журнала: 2022, Номер 12(1)
Опубликована: Июль 14, 2022
Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists causal association the effect direction remains unknown. To examine causative role of in risk disorders, we estimated their genetic correlation, then conducted two-sample Mendelian randomization analysis using summary statistics from genome-wide studies susceptibility, hospitalization, severity COVID-19, as well six major disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body multiple Parkinson's disease. We identified significant positive hospitalization AD (genetic correlation: 0.23, P = 8.36E-07). Meanwhile, was significantly associated with higher (OR: 1.02, 95% CI: 1.01-1.03, P: 1.19E-03). Consistently, susceptibility 1.05, 1.01-1.09, 9.30E-03) 1.01, 1.00-1.02, 0.012) were nominally AD. The results robust under all sensitivity analyses. These demonstrated that could increase Future development preventive or therapeutic interventions attach importance to this alleviate complications COVID-19.
Язык: Английский
Процитировано
105
Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16
Опубликована: Апрель 12, 2024
Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.
Язык: Английский
Процитировано
89
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Март 15, 2024
Mounting evidence progressively appreciates the vital interplay between immunity and metabolism in a wide array of immunometabolic chronic disorders, both autoimmune non-autoimmune mediated. The immune system regulates functioning cellular within organs like brain, pancreas and/or adipose tissue by sensing adapting to fluctuations microenvironment’s nutrients, thereby reshaping metabolic pathways that greatly impact pro- or anti-inflammatory immunophenotype. While it is agreed relies on an adequate nutritional status function properly, we are only just starting understand how supply single combined all them termed immunonutrients, can steer cells towards less inflamed, tolerogenic Polyphenols, class secondary metabolites abundant Mediterranean foods, pharmacologically active natural products with outstanding immunomodulatory actions. Upon binding range receptors highly expressed (e.g. AhR, RAR, RLR), they act through mitochondria-centered multi-modal approach. First , polyphenols activate nutrient via stress-response pathways, essential for responses. Second regulate mammalian target rapamycin (mTOR)/AMP-activated protein kinase (AMPK) balance well-tolerated caloric restriction mimetics. Third interfere assembly NLR family pyrin domain containing 3 (NLRP3) endoplasmic reticulum-mitochondria contact sites, inhibiting its activation while improving mitochondrial biogenesis autophagosome-lysosome fusion. Finally chromatin remodeling coordinates epigenetic reprogramming. This work moves beyond well-documented antioxidant properties polyphenols, offering new insights into multifaceted nature these compounds. It proposes mechanistical appraisal regulatory which modulate response, alleviating low-grade inflammation. Furthermore, draws parallels pharmacological interventions polyphenol-based immunonutrition their modes immunomodulation across spectrum socioeconomically impactful diseases such as Multiple Sclerosis, Diabetes (type 1 2) even Alzheimer’s disease. Lastly, discusses existing challenges thwart translation polyphenols-based immunonutritional long-term clinical studies. Overcoming limitations will undoubtedly pave way precision nutrition protocols provide personalized guidance tailored plans.
Язык: Английский
Процитировано
23
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4297 - 4297
Опубликована: Фев. 21, 2023
Aging reduces homeostasis and contributes to increasing the risk of brain diseases death. Some principal characteristics are chronic low-grade inflammation, a general increase in secretion proinflammatory cytokines, inflammatory markers. Aging-related include focal ischemic stroke neurodegenerative such as Alzheimer’s disease (AD) Parkinson’s (PD). Flavonoids most common class polyphenols abundantly found plant-based foods beverages. A small group individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, myricetin) has been used explore anti-inflammatory effect vitro studies animal models AD PD, results show that these reduce activated neuroglia several also, inactivate inflammation inflammasome-related transcription factors. However, evidence from human limited. In this review article, we highlight natural can modulate neuroinflammation diverse clinical discuss future areas research help researchers develop new therapeutic agents.
Язык: Английский
Процитировано
24
The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2024, Номер 12(4), С. 849 - 862
Опубликована: Фев. 12, 2024
Язык: Английский
Процитировано
12
Aging and Disease, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting an up-regulation of response at level, contributes to pathogenesis age-related neurodegenerative disorders. Development this proinflammatory state involves interaction between genetic environmental factors, able induce epigenetic modifications. Indeed, exposure compounds, drugs, infections, can contribute modifications DNA methylome, histone fold proteins, nucleosome positioning, leading modulation neuroinflammatory responses. Furthermore, some modifiers, which combine interact during life course, modeling epigenome dynamics sustain, or dampen phenotype. The aim review summarize current knowledge about neuroinflammaging with particular focus on mechanisms underlying onset progression cascades central nervous system; furthermore, we describe diagnostic biomarkers that may increase accuracy help tailor therapeutic strategies patients diseases.
Язык: Английский
Процитировано
10
Pharmacological Reviews, Год журнала: 2024, Номер 76(3), С. 323 - 357
Опубликована: Фев. 8, 2024
Over the last six decades, lithium has been considered gold standard treatment for long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways biologic systems, precise mechanism through which stabilizes mood remains elusive. Furthermore, there is recent support therapeutic potential other brain diseases. This review offers a comprehensive examination contemporary understanding predominant theories concerning diverse mechanisms underlying lithium's effects. These findings are based investigations utilizing animal models neurodegenerative psychiatric disorders. Recent studies have provided additional significance glycogen synthase kinase-3 (GSK3) inhibition crucial mechanism. research shed more light interconnections between GSK3-mediated neuroprotective, antioxidant, neuroplasticity processes. Moreover, advancements human valuable insights into how lithium-induced modifications at homeostatic synaptic plasticity level may play pivotal role clinical effectiveness. We focused from translational suggesting that interface with microRNA expression. Finally, we exploring repurposing beyond disorder. important clues toward developing predictive response identifying new targets.
Язык: Английский
Процитировано
9
Clinical Epigenetics, Год журнала: 2025, Номер 17(1)
Опубликована: Янв. 24, 2025
Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on biological functions associated with NDs, emphasizing role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed molecular underpinnings effects EE, including modulation key signaling pathways such extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), AMPK/SIRT1, which were implicated neuroprotection synaptic plasticity. Additionally, we scrutinized influence epigenetic modifications autophagy, processes pivotal ND pathogenesis. Animal models, encompassing both rodents larger animals, offer insights into disease-modifying underscoring complementary approach pharmacological interventions. In summary, emerges promising strategy augment function decelerate progression NDs.
Язык: Английский
Процитировано
1
eLife, Год журнала: 2024, Номер 12
Опубликована: Март 21, 2024
For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most neurodegenerative studies focus neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell types’ contribution. By unifying spatial gene expression, structural MRI, deconvolution, here describe how the human distribution canonical types extensively predicts tissue damage in 13 conditions, including early- late-onset Alzheimer’s disease, Parkinson’s dementia with Lewy bodies, amyotrophic lateral sclerosis, mutations presenilin-1, 3 clinical variants frontotemporal lobar degeneration (behavioral variant, semantic non-fluent primary progressive aphasia) along associated three-repeat four-repeat tauopathies TDP43 proteinopathies A C. We reconstructed whole-brain reference maps cellular abundance for six identified characteristic axes overlapping atrophy. Our results support strong mediating role non-neuronal cells, primarily microglia astrocytes, vulnerability to loss neurodegeneration, distinct shared across-disorder pathomechanisms. These observations provide critical insights into multicellular pathophysiology underlying spatiotemporal advance neurodegeneration. Notably, they also emphasize need exceed current neuro-centric view diseases, supporting imperative cell-specific therapeutic targets
Язык: Английский
Процитировано
7
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11638 - 11638
Опубликована: Окт. 30, 2024
Neuroinflammation, characterised by the activation of immune cells in central nervous system (CNS), plays a dual role both protecting against and contributing to progression neurodegenerative diseases, such as Alzheimer's disease (AD) multiple sclerosis (MS). This review explores phosphoinositide 3-kinase (PI3K), key enzyme involved cellular survival, proliferation, inflammatory responses, within context neuroinflammation. Two PI3K isoforms interest, PI3Kγ PI3Kδ, are specific regulation CNS cells, microglia, astrocytes, neurons, oligodendrocytes, influencing pathways, Akt, mTOR, NF-κB, that control cytokine production, cell activation, neuroprotection. The dysregulation signalling is implicated chronic neuroinflammation, exacerbation diseases. Preclinical studies show promise targeting neuronal disorders using inhibitors, AS605240 (PI3Kγ) idelalisib (PI3Kδ), which have reduced inflammation, microglial death vivo models AD. However, clinical translation these inhibitors faces challenges, including blood-brain barrier (BBB) permeability, isoform specificity, long-term safety concerns. highlights therapeutic potential modulation neuroinflammatory identifying gaps current research, particularly need for brain-penetrating isoform-specific inhibitors. These findings underscore importance future research develop targeted therapies can effectively modulate activity provide neuroprotection disorders.
Язык: Английский
Процитировано
6