A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers

• 作者: Andreia Gomes Bruno Manadas Cristina Januário Diana Pires Graça Baltazar Inês Baldeiras Luiza Rosado Mário Grãos Miguel Castelo-Branco Patrícia Valério dos Santos Sandra I.Anjo
• 来源期刊: 转化神经变性病(英文)
• 学科: 医学
• 关键词: Mitochondrial-related proteins SWATH-MS Parkinson's disease Biomarker discovery Blood-biomarker Secretomes Oxidative stress
• 年，卷（期）: zhsjbxbyw,（2）
• 页码范围: 118-131
• 页数: 14页
• 分类号: R74

摘要

Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the past.Nevertheless,in this pilot study,a translational approach was conducted,allowing the evaluation of the plasma levels of two mitochondrial-related proteins,whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls.Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions,followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states.This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients.Results From the secretome analysis,several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes.Similarly,two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls.Moreover,a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins.Both proteins are associated with apoptotic mitochondrial changes,which may correspond to potential indicators of cell death.Moreover,one of these proteins,the VPS35 protein,was reported in plasma for the first time,and its quantification was only possible due to its previous identification in the secretome analysis.Conclusions In this work,an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases,in the present case Parkinson’s Disease.The novelty and success of this pilot study may arise from the combination of:i)a translational research pipeline,where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’secret