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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/101632026-10-18T21:13:10Zopenairedrivercom_ebyu_10000col_ebyu_10001

Astaxanthin-Loaded Silver Nanoparticles Mitigate 6-OHDA-Induced Parkinson’s via ER Stress and PI3K/Akt/mTOR SignalingKara, HulyaTekiner, DenizÜstündağ, HilalBayram, CemilŞebin, Saime ÖzbekÖzkanlar, SeçkinKara, AdemAstaxanthinBrainDopamineParkinson’s diseaseRatSilver nanoparticleAnimalsCell Line, TumorEndoplasmic Reticulum StressHumansMaleMetal NanoparticlesNeuroprotective AgentsOxidative StressOxidopamineParkinson DiseasePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionSilverTOR Serine-Threonine KinasesXanthophyllsactivating transcription factor 6astaxanthin loaded silver nanoparticlebeta actincaspase 3cyclic AMP responsive element binding proteingamma interferonParkinson’s disease (PD) is characterized by progressive dopaminergic neuronal loss, with oxidative stress and neuroinflammation as critical pathological mechanisms. The blood–brain barrier presents a significant challenge for therapeutic delivery, while current treatments provide only symptomatic relief without halting disease progression. This study investigated the neuroprotective effects of astaxanthin-loaded citrate-coated silver nanoparticles (AST-AgNPs), leveraging their potent antioxidant properties, anti-inflammatory capacity, and enhanced blood–brain barrier penetration. In vitro cytotoxicity analyses were performed using 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y neuroblastoma cells, while in vivo experiments utilized a unilateral 6-OHDA-induced rat model. Following 14 days of treatment, comprehensive evaluations included behavioral assessments, biochemical analyses (MDA, GSH, SOD, TNF-α, IL-1β, IFN-γ), histopathology, immunohistochemistry (BrdU, tyrosine hydroxylase), and molecular analyses. Western blot measured CHOP, IRE1, ATF6, p-AKT, total AKT, caspase-3, and cleaved caspase-3, while RT-PCR quantified caspase-3, Bcl-2, Bax, PI3K, mTOR, Akt, CREB, and NF-κB-p65 expression. AST-AgNP treatment significantly ameliorated motor dysfunction, reduced neuroinflammation (TNF-α, IL-1β), improved oxidative stress parameters (MDA, GSH, SOD), and preserved dopaminergic neurons (all p < 0.05). Western blot revealed significant downregulation of ER stress markers (CHOP, IRE1, ATF6) and cleaved caspase-3, while restoring p-AKT and total AKT levels (p < 0.05). RT-PCR demonstrated decreased pro-apoptotic gene expression (caspase-3, NF-κB-p65) and increased anti-apoptotic Bcl-2 expression (p < 0.05). These findings demonstrate that AST-AgNPs provide neuroprotection through simultaneous modulation of ER stress and PI3K/Akt/mTOR pathways, representing a novel dual-pathway therapeutic strategy for PD addressing multiple pathological mechanisms through enhanced nanoparticle-mediated delivery. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.Springer2026Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10163https://doi.org/10.1007/s12035-025-05279-50893-7648enMolecular Neurobiologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10163