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Protective effects of Hesperidin loaded polymeric nanoparticles on the progression of MPTP Induced Parkinson’s disease via targeting GPR43/NLRP3 signaling pathway: in vitro and in vivo studies

M. Singh (Prayagraj, India)

Meeting: 2025 International Congress

Keywords: 1-Methyl-4-phenylpyridinium (MPP+), Parkinsonism

Category: Parkinson's Disease (Other)

Objective: Emphasizing the G protein-coupled receptor 43 (GPR43) and the NLRP3 signaling pathway in both in vitro and in vivo models, this work studies the effect of hesperidin-loaded polymeric nanoparticles (HSP-PNPs) on PD progression.

Background: The condition is defined by the aggregation of α-synuclein (α-syn) and the death of dopaminergic (DA) neurons as accumulating data suggest to a substantial role of gut bacteria and their metabolites in the pathogenesis of Parkinson’s disease (PD).

Method: This work investigated the effects of HSP-PNPs on α-syn deposition, DA loss, and neuroinflammation using a mouse model generated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced SH-SY5Y cells with HSP-PNPs-treated, HSP-PNPs-treated, SH-SY5Y cells were investigated In vitro supernatant from STC-1 cells was given to SH-SY5Y cells; effects were assessed following NLRP3 or GPR43 knockdown. In vivo animals treated with either NLRP3 or GPR43 inhibitors according to HSP-PNPs showed motor deficits, α-synopathy, DA neuronal loss, and inflammatory responses.

Results: HSP-PNPss were found to worsen motor and gastrointestinal dysfunctions in PD models, therefore generating α-synopathy and neuroinflammation. Reducing the observed effects by inhibition of these molecules, the activation of the NLRP3 inflammasome by GPR43 became obvious as a basic pathogenic mechanism. By reducing α-syn buildup, DA loss, and inflammatory responses, such treatments underlined the important role of the HSP-PNPs/GPR43-NLRP3 pathway in PD.

Conclusion: The results of this work explain a critical link between gut-derived metabolic changes and neuroinflammation in PD by means of the HSP-PNPs/GPR43-NLRP3 pathway. Targeting this route offers a possible therapy option and advances our understanding of the role of the gut-brain axis in PD progression.

To cite this abstract in AMA style:

M. Singh. Protective effects of Hesperidin loaded polymeric nanoparticles on the progression of MPTP Induced Parkinson’s disease via targeting GPR43/NLRP3 signaling pathway: in vitro and in vivo studies [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/protective-effects-of-hesperidin-loaded-polymeric-nanoparticles-on-the-progression-of-mptp-induced-parkinsons-disease-via-targeting-gpr43-nlrp3-signaling-pathway-in-vitro-and-in-vivo-studies/. Accessed October 5, 2025.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/protective-effects-of-hesperidin-loaded-polymeric-nanoparticles-on-the-progression-of-mptp-induced-parkinsons-disease-via-targeting-gpr43-nlrp3-signaling-pathway-in-vitro-and-in-vivo-studies/

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