Objective: To investigate the neuroprotective effect of AUF-loaded nanoparticles in animal models of Parkinson’s disease by modulating GSK-3β/ Nrf2/HO-1 Signaling Pathways.

Background: Parkinson’s disease (PD) is the second most prevalent motor disorder in the world. The current therapies provide symptomatic treatment and are unable to cure the disease completely. Recently, researchers have focused on formulation development to sustain levodopa’s effect and reduce its side effects. Therefore, the research has repurposed the auranofin (AUF), which has shown neuroprotective effects against Alzheimer’s. But the lacuna associated with AUF is its less penetration in the brain.

Method: AUF-loaded chitosan lipid hybrid nanoparticles (NPs) were prepared and characterized for particle size, zeta potential, entrapment efficiency, in-vitro drug release, and scanning electron microscopy (SEM). Then the rats (n=10) were pretreated with Licl (50 mg/kg, i.p.), Snpp (40 µM/kg, i.p.), AUF and AUF NPs (5 & 10 mg/kg, orally) followed by rotenone (1.5 mg/kg, s.c.) for 28 days. The parameters of the behavioral (rotarod, catalepsy, open field test) were evaluated on the 27^th and 28^th. On the 29^th day, animals were sacrificed, and brains were isolated for biochemical (GSH, SOD, catalase, MDA, nitrite), neurochemical (dopamine), inflammatory markers (IL-1β, TNF-α), histopathology, and western blot analysis.

Results: The particle size and zeta potential polydispersity index were found to be 284. 95 nm, 42.2±4.3 mV and 25.26%, respectively. Spherical shape NPs were observed under SEM analysis and followed the pattern of Higuchi release kinetics for in-vitro drug release study. Administration of AUF NPs in rats significantly restored motor activity and increased antioxidant levels. Also, reduced histopathological changes in substantia nigra and phosphorylates GSK-3β to increase expression of Nrf2/HO-1 followed by antioxidant and anti-inflammatory effects.

Conclusion: The study concludes that developing AUF NPs increases AUF’s bioavailability in the rat brain and exerts neuroprotection via modulation of GSK-3β/ Nrf2/HO-1 signaling pathways. Thus, it could be used as a therapeutic approach in treating PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deciphering-the-role-of-auranofin-loaded-nanoparticles-against-rotenone-model-of-parkinsons-disease-via-gsk-3%ce%b2-nrf2-ho-1-signaling-pathways/