Editorial Material 2025 · 0 atıf

Astaxanthin-Loaded Silver Nanoparticles Mitigate 6-OHDA-Induced Parkinson's via ER Stress and PI3K/Akt/mTOR Signaling

Kara, Hulya, Tekiner, Deniz, Ustundag, Hilal, Bayram, Cemil, Sebin, Saime Ozbek, Ozkanlar, Seckin, Kara, Adem

Özet

Parkinson'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-alpha, IL-1 beta, IFN-gamma), 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-kappa B-p65 expression. AST-AgNP treatment significantly ameliorated motor dysfunction, reduced neuroinflammation (TNF-alpha, IL-1 beta), 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-kappa B-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.

Anahtar Kelimeler

Parkinson's disease Dopamine Astaxanthin Silver nanoparticle Brain Rat ENDOPLASMIC-RETICULUM STRESS UNFOLDED PROTEIN RESPONSE THERAPEUTIC STRATEGIES OXIDATIVE STRESS GENE-EXPRESSION PATHWAY DISEASE MOTOR NEUROINFLAMMATION NEURODEGENERATION

WoS Kategorileri

Neurosciences

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: MOLECULAR NEUROBIOLOGY
Yıl: 2025
Cilt: 63
Sayı: 1
ISSN: 0893-7648
eISSN: 1559-1182
DOI: 10.1007/s12035-025-05279-5
WoS UID: WOS:001621399700008

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