Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 195 - 218
Published: Nov. 29, 2024
Language: Английский
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 612 - 612
Published: May 10, 2024
Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to brain. While BBB serves as crucial protective barrier, it poses challenges delivering therapeutic agents their intended targets within brain parenchyma. To enhance for treatment of neurological diseases, several technologies circumvent have been developed last few years. Among them, nanoparticles (NPs) are one most versatile and promising tools. Here, we summarize characteristics NPs that facilitate penetration, including size, shape, chemical composition, surface charge, importantly, conjugation with various biological or synthetic molecules such glucose, transferrin, insulin, polyethylene glycol, peptides, aptamers. Additionally, discuss coating surfactants. A comprehensive overview common vitro vivo models NP penetration studies is also provided. The discussion extends discussing impairment under pathological conditions leveraging alterations delivery. Emphasizing need future uncover inherent properties NPs, review advocates role beyond systems calls efforts translating clinic therapeutics. Overall, stand out highly strategy precise targeting disorders.
Language: Английский
Citations
19
Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 17, 2025
Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced
Language: Английский
Citations
2
ACS Nano, Journal Year: 2024, Volume and Issue: 18(24), P. 15452 - 15467
Published: June 3, 2024
Type 2 diabetes (T2D), a prevalent metabolic disorder lacking effective treatments, is associated with lysosomal acidification dysfunction, as well autophagic and mitochondrial impairments. Here, we report series of biodegradable poly(butylene tetrafluorosuccinate-co-succinate) polyesters, comprising 1,4-butanediol linker varying ratios tetrafluorosuccinic acid (TFSA) succinic components, to engineer lysosome-acidifying nanoparticles (NPs). The synthesized NPs are spherical diameters ≈100 nm have low polydispersity good stability. Notably, TFSA NPs, which composed entirely TFSA, exhibit the strongest degradation capability superior acidifying properties. We further reveal significant downregulation vacuolar (H+)-ATPase subunits, responsible for maintaining acidification, in human T2D pancreatic islets, INS-1 β-cells under chronic lipotoxic conditions, tissues high-fat-diet (HFD) mice. Treatment restores function, activity, thereby improving function cells HFD mice lipid overload. Importantly, administration reduces insulin resistance improves glucose clearance. These findings highlight therapeutic potential T2D.
Language: Английский
Citations
11
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1069 - 1076
Published: May 17, 2024
The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. Obesity-related conditions like type 2 diabetes non-alcoholic fatty liver exacerbate this relationship. Peripheral lipid accumulation, particularly in liver, initiates a cascade inflammatory processes that extend brain, influencing critical regulatory regions. Ceramide palmitate, key components, along with transporters lipocalin-2 apolipoprotein E, contribute neuroinflammation by disrupting blood–brain barrier integrity promoting gliosis. insulin resistance further exacerbates brain neuroinflammation. Preclinical interventions targeting peripheral metabolism signaling pathways have shown promise reducing animal models. However, translating these findings clinical practice requires investigation into human subjects. In conclusion, dysfunction, inflammation, are integral neurodegeneration. Understanding complex mechanisms holds potential for identifying novel therapeutic targets improving outcomes diseases.
Language: Английский
Citations
10
Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 11, 2025
Editorial: Lipid Metabolism Dysregulation in Obesity-Related Diseases and Neurodegeneration Provisionally accepted
Language: Английский
Citations
1
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: March 10, 2025
Abstract Astrocytes are a major cell type in the central nervous system (CNS) that play key role regulating homeostatic functions, responding to injuries, and maintaining blood-brain barrier. also regulate neuronal functions survival by modulating myelination degradation of pathological toxic protein aggregates. have recently been proposed possess both autophagic activity active phagocytic capability which largely depend on sufficiently acidified lysosomes for complete cellular cargos. Defective lysosomal acidification astrocytes impairs their resulting accumulation debris, excessive myelin lipids, aggregates, ultimately contributes propagation neuroinflammation neurodegenerative pathology. Restoration impaired represent new neuroprotective strategy therapeutic direction. In this review, we summarize pathogenic factors, including neuroinflammatory signaling, metabolic stressors, lipid mediated toxicity, contribute impairment associated dysfunction astrocytes. We discuss astrocyte-mediated primarily context diseases along with other brain injuries. then highlight re-acidification as restore well degradative capacity conclude providing future perspectives phagocytes crosstalk CNS cells impart or effects.
Language: Английский
Citations
0
Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1288 - 1288
Published: July 31, 2024
The first objective is to highlight the lack of tools measure whether a given intervention affords neuroprotection in patients with Alzheimer’s or Parkinson’s diseases. A second aim present primary outcome measures used clinical trials cohorts neurodegenerative final discuss metabolomics using body fluids may lead discovery biomarkers neuroprotection. Information on related and disease registered since 2018 was collected. We analysed type selected assess efficacy, not terms since, as stated aims, there yet any marker Proteomic approaches plasma CSF have been proposed. PET could estimate extent lesions, but progression does necessarily correlate change tracer uptake. propose some alternatives based considering metabolome. new opportunity opens because impressive technological advances that allow detection, among others, metabolites mitochondrial function structure serum and/or cerebrospinal fluid; differentially concentrated can become reliable
Language: Английский
Citations
2
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: July 12, 2023
Abstract Type 2 diabetes (T2D), a prevalent metabolic disorder lacking effective treatments, is associated with lysosomal acidification dysfunction as well autophagic and mitochondrial impairments. Here, we report series of biodegradable poly(butylene tetrafluorosuccinate-co-succinate) (PBFSU) polyesters, comprising an 1,4-butanediol linker varying ratios tetrafluorosuccinic acid (TFSA) succinic components, to engineer new lysosome acidifying nanoparticles (NPs). Notably, TFSA NPs, which composed entirely TFSA, exhibit the strongest degradation capability superior property. We further reveal significant downregulation vacuolar (H+)-ATPase (V-ATPase) subunits, are responsible for maintaining acidification, in human T2D pancreatic islets INS-1 β-cells under lipotoxic condition. Treatment NPs counteracts lipotoxicity by restoring function, activity, along promoting glucose-stimulated insulin secretion. Administration high-fat diet mice improves glucose clearance reduces resistance. These findings highlight therapeutic potential T2D. Graphical Table Contents
Language: Английский
Citations
2
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Oct. 16, 2023
Abstract Background Tumor necrosis factor (TNF) receptor 1 (TNFR1) signaling mediates neuronal necroptosis in Alzheimer’s disease (AD). Interaction of TNFR1 axis with autolysosomal pathway and the accumulation necrosome molecules impaired lysosomes have been shown to lead necroptotic death. This has attributed terminal failure autophagic process, primarily due lysosomal degradation dysfunction. Being final determining step pathway, sufficient acidification as maintained by functional vacuolar (H+)-ATPase (V-ATPase) are required achieve complete toxic cellular components. Here, we aim investigate role defective mediating induced AD. Methods Neuropathological analysis human post-mortem AD brains was performed examine correlation between Specifically, probed for level V-ATPase subunits determine extent function. Cell-based assays were conducted understand effect activation driving defect, impairment, mitochondrial dysfunction, death SH-SY5Y neuroblastoma cells. Furthermore, applied lysosome-acidifying nanoparticles (AcNPs) whether restoration can rescue both TNF-treated cells APP NL-G-F knock-in mouse model Results We revealed that activated correlates dysfunction characterized downregulation autophagy p62 brains. In cell culture, showed first time is only treated TNF not other cytokines, contributing inhibition also illustrated there turnover, together reduced functions elevated reactive oxygen species, leading Importantly, demonstrated AcNPs restore acidification, activity, function, well NL- G-F mice. Conclusions Defective plays a key mediated necroptosis. opens avenues new therapeutic strategies target
Language: Английский
Citations
2
International Journal of Power Electronics and Drive Systems/International Journal of Electrical and Computer Engineering, Journal Year: 2024, Volume and Issue: 14(3), P. 2988 - 2988
Published: April 4, 2024
The increasing prevalence of Alzheimer's disease in older adults has raised significant concern recent years. Aware this challenge, research set out to develop predictive models that allow early identification people at risk for disease, considering several variables associated with the disease. To achieve objective, data mining techniques were employed, specifically decision tree algorithm, using RapidMiner Studio tool. sample explore modify model and assess (SEMMA) methodology was implemented systematically each stage development, ensuring an orderly structured approach. results obtained revealed 45.00% dementia present characteristics identify them as candidates confirmation a diagnosis In contrast, 52.78% those who do not have show no danger contracting conclusion research, it noted most patients diagnosed are than 65 years, indicating life tends trigger brain changes This finding underscores importance age key factor
Language: Английский
Citations
0