Arabian Journal of Chemistry, Год журнала: 2024, Номер 18(1), С. 106072 - 106072
Опубликована: Ноя. 30, 2024
Язык: Английский
Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102680 - 102680
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
2
Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Background Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading the formation of neurofibrillary tangles. The overactivation in microglia promotes release pro-inflammatory cytokines, results neuroinflammation. Additionally, elevated oxidative stress during AD stimulates pathway, neuronal loss. Objective Because signaling plays a significant role phosphorylation, targeting may be therapeutically beneficial by either preventing excessive activation pathway or altering its enhance neuroprotective effects AD. Methods This study employed structure-based virtual screening phytoconstituents from IMPPAT library. Subsequently, in-depth docking molecular dynamics (MD) simulation studies were implemented identify potential inhibitors with desirable pharmacological properties. Results Silandrin Hydroxytuberosone found higher affinity specificity than control molecule Tizaterkib. These compounds specifically bind substrate binding pocket interact crucial residues. Finally, elucidated evaluated using an all-atom MD analyze structural dynamics, compactness, hydrogen bond principal component analysis, free energy landscape. Conclusions suggested that can further exploited as lead molecules therapeutic development against ERK1-mediated
Язык: Английский
Процитировано
1
Trends in Molecular Medicine, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
4
TrAC Trends in Analytical Chemistry, Год журнала: 2025, Номер 185, С. 118173 - 118173
Опубликована: Фев. 3, 2025
Язык: Английский
Процитировано
0
Biotechnology Reports, Год журнала: 2025, Номер 45, С. e00881 - e00881
Опубликована: Фев. 8, 2025
Despite broad spectrum utility of Nardostachys jatamansi (D. Don) DC, little is known about the molecular processes that underlie its anti-Alzheimer action. To investigate targets and therapeutic potential N. for Alzheimer's disease (AD), we used Gas Chromatography-Mass Spectrometry (GC-MS), ADMET analysis, network pharmacology, differential gene expression docking, dynamics (MD) simulations. The STITCH database was creation protein-protein interaction while Cytoscape visualization Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment Gene Ontology (GO) term enrichment. Additionally, to intermolecular interactions between active chemicals target proteins, docking experiments were conducted using Blind on Achilles server. stability PS1 complex with Spirojatamol, further evaluated MD With Spirojatamol showing highest binding energy scores against (-6.9 kcal/mol), confirmed activity this metabolite AD formed a stable at 100 nanoseconds, according additional investigation Significant ligand-protein verified by free calculations MM/GBSA technique. PS1-Spirojatamol had ΔG: -36.95 ± 5.00 kcal/mol. By focusing several genes pathways, involved in AD, work reveals underpinnings behind possible use treatment AD.
Язык: Английский
Процитировано
0
RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel inhibitors based on rational design SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC50 = 1.65 ± 0.55 μM) low toxicity (HepaRG >100 μM). The Morris water maze experiment revealed could alleviate cognitive impairment induced by scopolamine mice. This study facilitates the further development more potent for treatment
Язык: Английский
Процитировано
0
ACS Nano, Год журнала: 2025, Номер unknown
Опубликована: Фев. 24, 2025
Alzheimer's disease (AD) is an incurable neurodegenerative disorder and closely related to abnormal phosphoproteoforms. The analysis of low-abundance phosphoproteoforms relies heavily on the enrichment phosphoproteins. However, existing phosphoprotein materials suffer from either low selectivity or coverage due unavoidable unspecific adsorption background proteins. Here, we propose a strategy nanostructure-enabled superhydrophilic surfaces synthesize Ti4+-functionalized nanostructured microparticles (SNMs-Ti4+) via emulsion interfacial polymerization process. In this process, hydrophilic hydrophobic monomers assemble into stable oil-in-water emulsion, producing with abundant phosphate nanoprotrusions surface. are subsequently functionalized Ti4+. SNMs-Ti4+ exhibit enormous Ti4+ modifications, which allow effectively adsorb phosphoproteins suppress Using these SNMs-Ti4+, identified 2256 HeLa cells, twice number those enriched commercial kits. From AD mouse brains, 2603 were successfully enriched, 10 times AD-related differentially regulated discovered than without enrichment. These show great prospects for biomarker detection, diagnosis, downstream biological process disclosure.
Язык: Английский
Процитировано
0
Chemico-Biological Interactions, Год журнала: 2025, Номер 412, С. 111459 - 111459
Опубликована: Март 5, 2025
Язык: Английский
Процитировано
0
Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 200 - 200
Опубликована: Март 18, 2025
The rising prevalence of Alzheimer’s disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, cardiovascular health are recognized contributors to AD, but how the age onset affects progression remains underexplored. This study investigates role early- versus late-onset (EOAD LOAD, respectively) in shaping trajectory cognitive decline. Leveraging data from Religious Orders Study Memory Aging Project (ROSMAP), two cohorts were established: individuals with early-onset AD those AD. Comprehensive analyses, including differential gene expression profiling, pathway enrichment, co-expression network construction, conducted identify distinct molecular signatures associated each cohort. Network modularity learning algorithms used discern inner structure networks their related functional features. Computed descriptors provided deeper insights influence at on biological
Язык: Английский
Процитировано
0
Neurogenetics, Год журнала: 2025, Номер 26(1)
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0