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Daily intranasal resveratrol-conjugated gold nanoparticles administration promotes neuroprotection and improves neurological outcome in the R6/2 mouse model of Huntington's disease.

PMID: 41513082 · DOI: 10.1016/j.expneurol.2026.115639 · Experimental neurology, 2026 · Emanuela Paldino, Emiliano Montalesi, Marco Fiocchetti, Flavia Dioguardi, Iole Venditti, Elena Olivieri, Maria Marino, F
📄 Abstract

Pan-apoptosis and involvement of the inflammatory process are the hallmarks of Huntington's disease (HD). Inflammation currently represents one of the potential therapeutic targets for slowing and fighting the pathological phenotype of HD. The immunomodulatory properties of natural compounds, such as resveratrol, have been demonstrated in various disease models and human clinical trials. In the present study, we evaluated the neuroprotective and anti-inflammatory effects of the daily intranasal administration of resveratrol-conjugated gold nanoparticles in awake R6/2 mice, the genetic animal model of HD. Transgenic mice were treated daily with resveratrol-conjugated gold nanoparticles (0.1 mg/kg/day) starting from 5 weeks of age corresponding to the prodromal stage of the disease. After sacrifice, histological and immunofluorescence studies were performed. We found that resveratrol treated R6/2 mice survived longer and displayed a significant partial recovery of motor performance compared with R6/2 mice that received the nanoparticles with vehicle. Primary outcome measures such as striatal atrophy, neuronal intranuclear inclusions, and modulation of microglial reaction revealed a neuroprotective effect of resveratrol conjugated gold nanoparticles. Resveratrol provided a significant increase of neuroglobin, a neuroprotective globin, along with activated CREB and BDNF in the mice medium spiny neurons, accompanied by a down modulation of neuroinflammation, which, combined, might explain the beneficial effects observed in this model. Our findings showed that nanoparticles loaded with a specific compound which acts on the mutated protein intranuclear inclusions and inflammatory components may represent a valid therapeutic strategy in slowing down the symptoms of HD neurodegeneration.

Confidence: 0.14 · 6 полей извлечено
Идентификация (6 полей)
Механизм действия (21 полей)
Mechanism
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Mutations (obesity/lean)
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Activity (obesity)
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Activity temporal
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Energy balance
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Appetite
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Fat metabolism
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Lipolysis
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Thermogenesis
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Muscle metabolism
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Inflammation
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Glucose metabolism
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AA metabolism
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Hormonal pathways
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Cell death
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Adipocyte fibrosis
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Upstream (biochem)
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Upstream (physiol)
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Downstream (biochem)
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Downstream (physiol)
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PTMs
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Экспрессия (8 полей)
Tissue expression
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In vitro
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In vivo
Daily intranasal administration of resveratrol-conjugated gold nanoparticles in R6/2 mice (genetic animal model of Huntington's disease) starting from 5 weeks of age. Treated mice showed longer survival, partial recovery of motor performance, reduced striatal atrophy, fewer neuronal intranuclear inclusions, modulation of microglial reaction, increased neuroglobin, activated CREB and BDNF, and down-modulation of neuroinflammation.
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In silico
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Genetic association
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Ex vivo
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Animal model
R6/2 transgenic mice (genetic model of Huntington's disease)
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Diet/model
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Клиника (11 полей)
Drug
resveratrol
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Indication
Huntington's disease
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Patient subgroups
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Safety concerns
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Off-target
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Trial stage
preclinical
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Pharma competitors
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AE severity
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MOA weight loss
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Endpoints
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Approved
False
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