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Proteomic analysis of substantia nigra reveals molecular insights into the neuroprotection effect of rosmarinic acid treatment in MPTP-induced mouse model of Parkinson's Disease.
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  • Sarag Presti da Silva,
  • Lucas Rodrigues-Ribeiro,
  • Vladimir Gorshkov,
  • Frank Kjeldsen,
  • Thiago Verano-Braga,
  • Rita Pires
Sarag Presti da Silva
Federal University of Espirito Santo
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Lucas Rodrigues-Ribeiro
Federal University of Minas Gerais
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Vladimir Gorshkov
University of Southern Denmark
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Frank Kjeldsen
PRgroup
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Thiago Verano-Braga
Universidade Federal de Minas Gerais
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Rita Pires

Corresponding Author:rita.pires@ufes.br

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Abstract

Parkinson’s disease (PD) is neuropathologically characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), affecting 10 million people worldwide. Rosmarinic acid (RA), a polyphenol found in plants like rosemary (Rosmarinus officinalis), is known for its intriguing biological properties and potential antioxidant and neuroprotective effects. In a previous study we showed that RA treatment prevented hyperlocomotion in mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced parkinsonism and improved the monoaminergic system in healthy animals. However, the molecular mechanisms underlying RA’s action in PD remain unclear. In this study, we treated MPTP-induced PD animals (C57BL/6 male mice) with RA orally at a dose of 100 mg/kg for 15 days and examined the proteome of substantia nigra (SN) to identify possible regulatory targets of RA treatment to shed some lights into its neuroprotective effects. Quantitative proteomics revealed that RA treatment regulated proteins associated with oxidative phosphorylation (OXPHOS), glutamatergic synapse, and vesicular cycle signaling pathway. We identified 371 proteins significantly regulated in response to RA administration (255 upregulated and 116 downregulated). Notably, some cellular targets of RA treatment reported here, including mGluR2/mGluR3/EAAT - proteins from the glutamatergic system - and proteins from the Complex I of the electron transport chain are promising targets for therapeutic intervention. These findings highlight the molecular differences between MPTP-induced PD mice and those treated with RA, providing insights on the molecular basis behind the neuroprotective effects of RA and revealing potential PD signatures that warrant further investigation.
18 Jul 2024Submitted to Clinical Applications
19 Jul 2024Submission Checks Completed
19 Jul 2024Assigned to Editor
19 Jul 2024Review(s) Completed, Editorial Evaluation Pending
19 Jul 2024Reviewer(s) Assigned