Biological Psychiatry, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Revista Brasileira de Farmacognosia, Год журнала: 2025, Номер unknown
Опубликована: Фев. 5, 2025
Язык: Английский
Процитировано
0
Brain Pathology, Год журнала: 2025, Номер unknown
Опубликована: Март 5, 2025
Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis essential for normal brain function. CYP46A1, crucial cholesterol turnover and reduced some neurodegenerative diseases, a potential neuroprotective target. We hypothesized that CYP46A1 downregulated MS brains dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma cerebrospinal fluid (CSF) an all-female cohort (n = 32, mean age 33). status recorded at baseline follow-up. tissue samples 11; 7 females; ages 38-67; 10 Secondary Progressive MS, 1 Primary MS; Disease Duration: 13-49 years) control 8; 3 41-68) analysed pathological regions using mass spectrometry RNA expression in-situ hybridization. Significant dysregulation 25-hydroxycholesterol, 27-hydroxycholesterol 3β-hydroxycholestenoic acid CSF correlated with disability follow-up the patient population. In tissue, cholesterol, 24S-hydroxycholesterol 24S,25-epoxycholesterol were observed white matter lesions (p < 0.05), activity. enriched neurons, reductions grey non-lesions compared controls 0.01). metabolism dysregulated associated neuron-specific expression. Modulating druggable target, may benefit progressive MS.
Язык: Английский
Процитировано
0
International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142414 - 142414
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)
Опубликована: Март 1, 2025
ABSTRACT Disruptions in the metabolism of cholesterol and other lipids are strongly implicated pathogenesis neurological disease. The CNS is highly enriched cholesterol, which primarily synthesized de novo . Cholesterol synthesis also rate limiting for myelin regeneration. Given that knockout thrombin receptor (Protease Activated Receptor 1 (PAR1)) accelerates regeneration, here we sought to determine potential regulatory actions PAR1 lipid intact adult during We present quantitative PCR RNAseq evidence from murine spinal cords at peak myelination adulthood showing associated with increased gene expression biosynthesis (Hmgcs1, Hmgcr, Sqle, Dhcr7), transport (ApoE, Abca1, Ldlr), intracellular processing (Lcat, Npc1, Npc2) one or more time points examined. An upregulation genes involved membrane, specifically Fa2h, Ugt8a, Gal3st1, was observed knockouts. Transcription factors essential production (Srebf1 Srebf2) were postnatal day 21 45. GC–MS LC–MS quantification demonstrated coordinate increases abundance select species mice, including enrichment esterified together sphingomyelins sphingolipids. Co‐localization SREBP1 SREBP2 transcription factors, as well HMGCS1, a rate‐limiting enzyme biosynthesis, glia remyelination post‐lysolecithin cuprizone‐mediated demyelination showed prominent role Olig2+ oligodendrocytes. knockouts elevated levels mature GST3+ oligodendrocytes GFAP+ astrocytes post‐lysolecithin. These findings demonstrate novel roles regulator its therapeutic target increase availability improve image
Язык: Английский
Процитировано
0
Expert Review of Neurotherapeutics, Год журнала: 2025, Номер unknown
Опубликована: Март 26, 2025
As the world population ages, Alzheimer disease (AD) prevalence increases. However, understanding of AD etiology continues to evolve, and pathophysiological processes involved are only partially elucidated. One compound suspected play a role in development progression is cholesterol. Several lines evidence support this connection, yet it remains unclear whether cholesterol-modifying strategies have potential applications clinical management AD. A deep literature search using PubMed was performed prepare narrative review. The search, early 2024, inclusive from 1990 2024. After providing an overview cholesterol metabolism, study summarizes key preclinical studies that investigated therapies laboratory models It also past current trials testing specific targets modulated by anti-cholesterol patients. Based on epidemiological mechanistic studies, likely plays etiology. use could be promising treatment approach if administered at presymptomatic phases, but unlikely efficient mild, moderate, late stages. recommendations provided for hypercholesterolemia
Язык: Английский
Процитировано
0
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Сен. 28, 2024
Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease. Microglia activation is accompanied by formation and chronic expression TLR4 inflammarafts, defined as enlarged cholesterol-rich lipid rafts serving assembly platform for dimers complexes other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds selectively targets cholesterol depletion machinery to inflammaraft-expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aβ) induced inflammarafts microglia vitro brain APP/PS1 mice. Mitochondria Apoa1bp
Язык: Английский
Процитировано
3
iScience, Год журнала: 2024, Номер 27(2), С. 109013 - 109013
Опубликована: Янв. 25, 2024
Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere neurodegeneration cognitive decline, have cholesterol-lowering, anti-inflammatory, antioxidant qualities. Here, we investigated the potential associations between circulating precursors metabolites, triglycerides, phytosterols with decline older people by performing multivariate analysis on 246 participants engaged a population-based prospective study. In our considered effect of sex APOEe4. We reveal particular diet-derived endogenous synthesis metabolism, their variations over time general population. These results significant development interventions avoid adults suggest that levels sterols should be taken into account when evaluating risk.
Язык: Английский
Процитировано
2
Irish Journal of Medical Science (1971 -), Год журнала: 2024, Номер unknown
Опубликована: Июнь 4, 2024
Abstract Introduction Aging is accompanied by changes in body composition, such as an increase fat mass (FM), a decrease skeletal muscle index (SMMI) and strength, combined with chronic inflammatory process (CI). Objective Determine the relationship between age excess markers of inflammation, strength. Methods A cross-sectional alitical study was carried out convenience sample adults 45 to 59 years old ( n = 100) older 60 74 133). All participants had their composition measured impedance meter. They were subsequently divided into two groups: (i) (WEF), (ii) without (NEF), order relate Results NEF similar values SMMI (9.1 ± 1.5 vs. 8.8 1.3, p > 0.05) strength (28 8 27 8.6, 0.05). Likewise, WEF showed significantly lower than (7.9 0.8 9.1 1.5, < 22 5, 0.001). Also, presented (15.9 1.8 22.8 5.1, (17.9 4.8 Conclusions Our findings suggest that risk factor has greater influence aging per se on
Язык: Английский
Процитировано
2
Biomolecules, Год журнала: 2024, Номер 14(11), С. 1362 - 1362
Опубликована: Окт. 26, 2024
Aging induces complex changes in the lipid profiles across different areas of brain. These can affect function brain cells and may contribute to neurodegenerative diseases such as Alzheimer's disease. Research shows that while overall profile human remains quite steady throughout adulthood, specific occur with age, especially after age 50. include a slow decline total content shifts composition fatty acids, particularly glycerophospholipids cholesterol levels, which vary depending on region. Lipid rafts play crucial role maintaining membrane integrity facilitating cellular signaling. In context disease, have been associated development For example, alterations raft lead increased accumulation amyloid β (Aβ) peptides, contributing neurotoxic effects. droplets store neutral lipids are key for energy metabolism. As organisms dynamics change, evidence suggesting metabolic activity over time. This reduced an imbalance synthesis mobilization, processes. model like Drosophila, studies shown metabolism be influenced by diet insulin signaling pathways, balance. The interplay between metabolism, oxidative stress, inflammation is critical aging peroxidation, consequence formation reactive aldehydes further damage neurons. Inflammatory processes also disrupt pathology AD. Consequently, oxidized integrity, influencing pathways involved neuronal survival function.
Язык: Английский
Процитировано
2
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Фев. 21, 2024
ABSTRACT Microglia-driven neuroinflammation plays an important role in the development of Alzheimer’s disease (AD). Microglia activation is accompanied by formation and chronic maintenance TLR4 inflammarafts, defined as enlarged cholesterol-rich lipid rafts serving assembly platform for dimers complexes other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds selectively targets cholesterol depletion machinery to inflammaraft expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aβ) induced inflammarafts microglia vitro brain APP/PS1 mice. Mitochondria Apoa1bp -/- were hyperbranched cupped, which was increased ROS dilated ER. size number Aβ plaques neuronal cell death significantly increased, animal survival decreased compared female These results suggest AIBP exerts control mitochondrial dynamics a protective AD associated oxidative stress neurodegeneration.
Язык: Английский
Процитировано
1