Understanding of Alzheimer's Disease Pathophysiology for Therapeutic Implications of Natural Products as Neuroprotective Agents

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102680 - 102680

Published: Feb. 1, 2025

Language: Английский

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Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: Английский

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Advancements and challenges in mouse models of Alzheimer’s disease

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Surface-enhanced Raman scattering for the detection of biomarkers of neurodegenerative diseases: A review

TrAC Trends in Analytical Chemistry, Journal Year: 2025, Volume and Issue: 185, P. 118173 - 118173

Published: Feb. 3, 2025

Language: Английский

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Integration of Phytochemical Profiling and Computational Approaches to Evaluate the Neuroprotective Potential of Nardostachys jatamansi in Alzheimer's Disease

Biotechnology Reports, Journal Year: 2025, Volume and Issue: 45, P. e00881 - e00881

Published: Feb. 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.

Language: Английский

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Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitor for the treatment of Alzheimer's Disease

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: Английский

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Superhydrophilic Nanostructured Microparticles for Enhanced Phosphoprotein Enrichment from Alzheimer’s Disease Brain

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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The anti-Alzheimer's Disease effects of ganoderic acid A by inhibiting ferroptosis-lipid peroxidation via activation of the NRF2/SLC7A11/GPX4 signaling pathway

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: 412, P. 111459 - 111459

Published: March 5, 2025

Language: Английский

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Gene Co-Expression Analysis Reveals Functional Differences Between Early- and Late-Onset Alzheimer’s Disease

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 200 - 200

Published: March 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

Language: Английский

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Multi-target approach to Alzheimer’s disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 1, 2025

Language: Английский

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