Published: June 14, 2024
Language: Английский
MedComm, Journal Year: 2024, Volume and Issue: 5(2)
Published: Feb. 1, 2024
Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset cardiovascular disease (CVD) but also fundamental cause other ailments. regulation in human an extremely complex process. Due to dynamic balance between synthesis, intake, efflux storage, generally remains secure. Disruption any these links likely have adverse effects on body. At present, increasing evidence suggests that abnormal closely related various diseases. However, exact mechanism by which contributes pathogenesis unclear, there are still unknown factors. In this review, we outline metabolic process body, especially reverse transport (RCT). Then, discuss separately impact common diseases potential therapeutic targets each disease, including CVD, tumors, neurological diseases, immune system end focus effect eye short, hope provide more new ideas treatment from perspective cholesterol.
Language: Английский
Citations
26
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3892 - 3892
Published: March 31, 2024
The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that protein amyloid-beta cause of disease. Two antibodies, aducanumab and lecanemab, have been approved by U.S. Food Drug Administration, while a third, donanemab, under review. main argument FDA approvals presumed therapy-induced removal cerebral deposits. Lecanemab donanemab are also thought to some statistical delay in determination cognitive decline. However, clinical efficacy less than with conventional treatment, selection amyloid-positive trial patients non-specific amyloid-PET imaging, uncertain amyloids trials cast doubt on this anti-Alzheimer's antibody therapy hence hypothesis, calling more thorough investigation negative impact type brain.
Language: Английский
Citations
17
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Nov. 8, 2023
Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1
Language: Английский
Citations
20
Life Sciences, Journal Year: 2024, Volume and Issue: 340, P. 122457 - 122457
Published: Jan. 23, 2024
Language: Английский
Citations
8
Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2052 - 2052
Published: July 31, 2023
Alzheimer disease (AD) is the most prevalent form of dementia among elderly people. Owing to its varied and multicausal etiopathology, intervention strategies have been highly diverse. Despite ongoing advances in field, efficient therapies mitigate AD symptoms or delay their progression are still limited scope. Neuroplasticity, broad terms ability brain modify structure response external stimulation damage, has received growing attention as a possible therapeutic target, since disruption plastic mechanisms appear correlate with various forms cognitive impairment present patients. Several pre-clinical clinical studies attempted enhance neuroplasticity via different mechanisms, for example, regulating glucose lipid metabolism, targeting activity neurotransmitter systems, addressing neuroinflammation. In this review, we first describe several structural functional aspects neuroplasticity. We then focus on current status pharmacological approaches stemming from trials neuroplastic This followed by an analysis analogous interventions animal models, according action.
Language: Английский
Citations
14
Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)
Published: July 28, 2024
Alzheimer's disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate blood-brain barrier exert anti-inflammatory effects central nervous system. Here, we investigate protective long-term NRG treatment on AD. The novel object recognition test Morris water maze reveal that improve learning memory ability APP/PS1 mice. Besides, find significantly reduce Aβ microglial astrocytic activation, pro-inflammatory cytokine levels Results further show effectively decreases cytokines LPS/Aβ-stimulated BV2 cells. Lastly, molecular mechanistic study reveals attenuates neuroinflammatory responses via inhibition MAPK signaling pathway vivo vitro. Overall, may emerge as promising compound for prevention A naringenin disease, including reducing decreasing responses, improving cognitive function
Language: Английский
Citations
4
Bioengineering, Journal Year: 2023, Volume and Issue: 10(7), P. 871 - 871
Published: July 23, 2023
Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.
Language: Английский
Citations
11
Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2595 - 2595
Published: Nov. 9, 2023
Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world are insidious in onset, chronic nature, yield significant disability death. Current therapies that address nutritional status, weight management, pharmacological options may delay but cannot alter disease course or functional organ loss, such as dementia degeneration of systemic bodily functions. Underlying these challenges onset aging associated with increased lifespan, telomere dysfunction, oxidative stress generation lead to multi-system dysfunction. These hurdles point urgent need underlying mechanisms innovative applications. New treatment strategies involve non-coding RNA pathways microRNAs (miRNAs) circular ribonucleic acids (circRNAs), Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1) dependent upon programmed cell death pathways, cellular metabolic AMP-activated kinase (AMPK) nicotinamide, growth factor Non-coding RNAs, AMPK cornerstone for overseeing complex offer avenues DM will necessitate continued appreciation ability each independently unison influence clinical outcome.
Language: Английский
Citations
11
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 312 - 312
Published: Jan. 1, 2025
Objective: The objective of this study was to explore the possibility treating heart failure in rats by delivering mRNA 24-dehydrocholesterol reductase (DHCR24) into body through lipid nanoparticles (LNPs). Methods: We established a rat model using doxorubicin. experiment divided blank, model, stock solution cardiac injection, intravenous LNP-mRNA and injection groups. directly injected DHCR24-mRNA or LNP-DHCR24-mRNA myocardium three regions an insulin needle passing intercostal space under guidance B-ultrasound. recorded mortality rate, weight, 6-min walk test return times, organ weight after administration detected structure function B-ultrasound transmission electron microscopy (TEM). Additionally, we tested for HE staining; PRDX2, Sirt3, TRX1 protein expression; IL-1 β, IL-10, VEGF, NT proBNP, BNP cytokine concentrations. Results: Compared with group, significantly reduced mortality; decreased loss, ratio tibia length, spleen weight; improved motility. can postpone pathological morphological alterations myocardial cells reduce inflammatory infiltration. In terms biochemistry, increase expression proteins; concentrations IL-10 VEGF; IL-1β, BNP. also delay process failure. delivery therapeutic effect encapsulated LNPs were better when compared other Conclusions: be effectively administered exhibits some curative effects.
Language: Английский
Citations
0
Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)
Published: Jan. 20, 2025
Background: Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer’s disease (AD). However, underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal function, whereas disrupted SV can trigger associated with AD. In this study, we investigated whether cellular affects mobility, aim of identifying mechanism that links loss Methods: Lentiviruses carrying 3β-hydroxysteroid-Δ24 reductase-complementary DNA (DHCR24-cDNA), DHCR24-short hairpin RNA (DHCR24- shRNA) or empty lentiviral vectors were transfected into SHSY-5Y cells order construct DHCR24 knock-down and knock-in models, along corresponding controls. Filipin III staining was employed visualize membrane intracellular different cell fluorescence intensity assessed using confocal microscopy. Additionally, performed immunoblotting quantify expression DHCR24, total calmodulin-dependent protein kinase 2 (CAMK-2), p-CAMK2 (T286), caveolin-1, synapsin-1, phosphorylated synapsin-1 (p-synapsin-1; S605), synaptophysin each experimental group. Results: DHCR24-silenced cells, caused by DCHR24 resulted a significant decrease levels CAMK2 (p-CAMK2) (p-synapsin-1) compared control cells. The reduction p-synapsin-1 could disrupt thereby reducing replenishment readily releasable pool (RRP) from reserve (RP). Furthermore, showed downregulation lipid raft marker, Conversely, elevated reversed effects deficiency, suggesting CAMK2-mediated phosphorylation be regulated raft-associated manner. found significantly downregulate protein, which vital biogenesis plasticity. Conclusion: These results suggest depletion following impair regulating CAMK2-meditated pathway, potentially via mechanism. Our study indicates critical role AD-related synaptopathy, thus highlighting potential targeting metabolism therapeutic strategies.
Language: Английский
Citations
0