Work

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

Year: 2025

Type: article

Abstract: PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Source: PROTEOMICS - CLINICAL APPLICATIONS

DOI: 10.1002/prca.70006

Authors: Sarah Martins Presti‐Silva, Lucas Rodrigues‐Ribeiro, Vladimir Gorshkov, Frank Kjeldsen, Thiago Verano‐Braga, Rita Gomes Wanderley Pires

Institutions: Universidade Federal de Minas Gerais, Universidade Federal do Espírito Santo, Instituto Nacional de Ciência e Tecnologia em Nano-Biofarmacêutica, University of Southern Denmark

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green