Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 13, 2025

Lipid droplets (LDs), serving as the convergence point of energy metabolism and multiple signaling pathways, have garnered increasing attention in recent years. Different cell types within central nervous system (CNS) can regulate to generate or degrade LDs response diverse pathological stimuli. This article provides a comprehensive review on composition CNS, their generation degradation processes, interaction mechanisms with mitochondria, distribution among different types, roles played by these cells-particularly microglia astrocytes-in various prevalent neurological disorders. Additionally, we also emphasize paradoxical role post-cerebral ischemia inflammation explore potential underlying mechanisms, aiming identify novel therapeutic targets for this disease.

Язык: Английский

---

Downregulation of the SREBP pathways and disruption of redox status by 25-hydroxycholesterol predispose cells to ferroptosis

Free Radical Biology and Medicine, Год журнала: 2025, Номер 228, С. 319 - 328

Опубликована: Янв. 7, 2025

Enzymatically formed side-chain oxysterols function as signaling molecules regulating cholesterol homeostasis and act intermediates in the biosynthesis of bile acids. In addition to these physiological functions, an imbalance oxysterol has been implicated pathophysiology. Cholesterol 25-hydroxylase (CH25H) its product 25-hydroxycholesterol (25-OHC), also by autoxidation, are associated with amyotrophic lateral sclerosis. However, effects 25-OHC on cell viability glial cells remain unclear. This study demonstrates that induces ferroptosis, iron-dependent programmed death, mouse Schwann IMS32 cells. Mechanistically, suppressed expression selenoprotein glutathione peroxidase 4 (GPX4) at both transcriptional translational levels inhibiting processing sterol regulatory element-binding proteins (SREBPs). addition, upregulated NADH-cytochrome b5 reductase 1 (CYB5R1) NADPH-cytochrome P450 (POR), enzymes promote lipid peroxidation. We further found increases glutathione-specific gamma-glutamylcyclotransferase (CHAC1) decreases levels. Importantly, non-cytotoxic concentrations enhanced cellular sensitivity ferroptosis inducers downregulating GPX4 expression. These findings reveal a multifaceted approach whereby through SREBP pathway suppression redox

Язык: Английский

---

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction

Pflügers Archiv - European Journal of Physiology, Год журнала: 2025, Номер 477(3), С. 421 - 439

Опубликована: Янв. 9, 2025

Язык: Английский

---

Regulation of osteoclast-mediated bone resorption by lipids

Bone, Год журнала: 2025, Номер 193, С. 117423 - 117423

Опубликована: Фев. 9, 2025

Язык: Английский

---

Lipid-targeting antiviral strategies: current state and future perspectives

Antiviral Research, Год журнала: 2025, Номер unknown, С. 106103 - 106103

Опубликована: Фев. 1, 2025

Язык: Английский

---

Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 27, 2025

Cholesterol, the most abundant sterol molecule in mammalian organisms, serves not only as a fundamental structural component of cell membranes but also critical regulator cellular signaling and function. Cholesterol-associated proteins can mediate liver injury either directly by influencing cholesterol levels or through non-cholesterol pathways. These pathways, which operate independently cholesterol’s traditional metabolic functions, are regulated specific transcription factors, receptors. Dysregulation cholesterol-associated disrupt homeostasis, leading to injury, disorders, even tumorigenesis. In this article, we explore mechanisms contribute via both classical pathways discuss their potential therapeutic targets for liver-related diseases.

Язык: Английский

---

25-Hydroxycholesterol attenuates tumor necrosis factor alpha-induced blood-brain barrier breakdown in vitro

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(8), С. 167479 - 167479

Опубликована: Авг. 23, 2024

Intracellular cholesterol metabolism is regulated by the SREBP-2 and LXR signaling pathways. The effects of inflammation on these molecular mechanisms remain poorly studied, especially at blood-brain barrier (BBB) level. Tumor necrosis factor α (TNFα) a proinflammatory cytokine associated with BBB dysfunction. Therefore, aim our study was to investigate TNFα metabolism, focusing its underlying Using human in vitro model composed brain-like endothelial cells (hBLECs) brain pericytes (HBPs), we observed that increases permeability degrading tight junction protein CLAUDIN-5 activating stress pathways both cell types. also promotes release decreases accumulation APOE secretion. In hBLECs, expression targets (LDLR HMGCR) increased, while ABCA1 decreased. HBPs, only LDLR increased. treatment induces 25-hydroxycholesterol (25-HC) production, metabolite involved immune response intracellular metabolism. 25-HC pretreatment attenuates TNFα-induced leakage partially alleviates ABCA1, LDLR, HMGCR expression. Overall, results suggest favors efflux via an LXR/ABCA1-independent mechanism BBB, it activates pathway. Treatment reversed effect LXR/SREBP-2 Our provides novel perspectives for better understanding cerebrovascular events linked dysfunction neuroinflammatory diseases.

Язык: Английский

---

Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells.

Neuropharmacology, Год журнала: 2025, Номер unknown, С. 110294 - 110294

Опубликована: Янв. 1, 2025

The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic NMDA glutamatergic receptors in neurons. has been shown also purinergic (P2X) are metabolites' targets. Among P2X receptors, P2X4 P2X7 expressed microglia, the innate immune cells involved brain inflammatory response. In this study, we explore modulation by microglia. Patch-clamp experiments were performed BV2 cells, murine microglia cell line, to evaluate effects of using micro- nanomolar concentrations. About receptor, found testosterone butyrate (20 μM 200 nM) allopregnanolone (10 100 both potentiated its current, while neither 25-hydroxycholesterol nor 17β-estradiol (1 μM) showed any effects. On other hand, current was nM). Taken together, our data show either affected differently metabolites, suggesting structure-activity relationship players. Identifying possible link between transmission, will allow define new targets for drug development treat neuroinflammation.

Язык: Английский

---

Integrated microbiome and metabolome analysis reveals altered gut microbial communities and metabolite profiles in dairy cows with subclinical mastitis

BMC Microbiology, Год журнала: 2025, Номер 25(1)

Опубликована: Март 4, 2025

Dairy cow mastitis is a common and prevalent disease arose by various complicated pathogeny, which poses serious threat to the health of cows, safety dairy product economic benefits for pastures. Due high stealthiness long incubation period, subclinical (SM) cows causes enormous losses. Besides infection exogenous pathogenic microorganisms, previous studies demonstrated that gastrointestinal microbial dysbiosis one crucial occurrence development based on theory entero-mammary axis. Whereas, limited researches have been conducted potential pathological metabolic mechanisms underlying relationship between gut microbiota SM in cows. The differences blood parameters, microbiome, plasma fecal metabolome healthy were compared performing 16 S rDNA sequencing non-targeted metabolomic analysis current study. content total cholesterol (TC), high-density lipoprotein (HDL-C), activity catalase (CAT), antioxidant capacity(T-AOC) significantly decreased, while malondialdehyde (MDA) concentration was dramatically increased serum comparison with harbored more abundant Cyanobacteria, Proteobacteria, Succinivibrio Lactobacillus_iners. Moreover, abundance Paraprevotella, Coprococcus, Succiniclasticum, Desulfovibrio Bifidobacterium_pseudolongum observably reduced Furthermore, higher pro-inflammatory metabolites observed feces (9(S)-HPODE, 25-hydroxycholesterol, dodecanedioic acid, etc.) (9-hydroxy-10,12-octadecadienoic 13,14-dihydro PGF1α, 5,6-dehydro arachidonic myristic histamine, certain anti-inflammatory properties (mandelic gamma-tocotrienol, deoxycholic notably decreased or SM. intestinal composition profiles distinct, characterized symbiotic bacteria, probiotics anti-inflammatory, compounds, along lipid metabolites, oxidative stress suffered from results this study further enriched our understanding correlations SM, provided insight into formulation management strategies

Язык: Английский

---

Associations Between Follicular Fluid Biomarkers and IVF/ICSI Outcomes in Normo-Ovulatory Women—A Systematic Review

Biomolecules, Год журнала: 2025, Номер 15(3), С. 443 - 443

Опубликована: Март 20, 2025

(1) Background: The follicular fluid (FF) comprises a large portion of ovarian follicles, and serves as both communication growth medium for oocytes, thus should be representative the metabolomic status follicle. This review aims to explore FF biomarkers well their effects on fertilization, oocyte, embryo development, later implantation maintenance pregnancy. (2) Methods: was registered in PROSPERO database with ID: CRD42025633101. We parsed PubMed, Scopus, Google Scholar research different IVF/ICSI outcomes normo-ovulatory women. Included studies were assessed risk bias using NOS scale. Data extracted tabulated by two independent researchers. (3) Results: 22 included articles, sample size range 31 414 median 60 participants, contained 61 biomarkers, including proteins, factors, steroid polypeptide hormones, inflammation oxidative stress markers, amino acids, vitamins, lipids types, miRNAs. Most studied had significant outcomes, seem have roles various cellular pathways responsible oocyte growth, implantation, placental formation, metabolome also seems interconnected, its components influencing levels activities each other through feedback loops. (4) Conclusions: can utilized diagnostic therapeutic purposes IVF; however, further are required choosing most promising ones due heterogeneity results. Widespread adoption LC-MS miRNA microarrays help quantify metabolome, we see great potential vitro supplementation (IVS) some improving outcomes.

Язык: Английский

---