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.
Sarah Martins Presti-Silva, Lucas Rodrigues-Ribeiro, Vladimir Gorshkov, Frank Kjeldsen, Thiago Verano-Braga, Rita Gomes Wanderley Pires
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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.
期刊介绍：
PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including:
-basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease
-the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers
-the use of proteomics for the discovery of novel drug targets
-the application of proteomics in the drug development pipeline
-the use of proteomics as a component of clinical trials.
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