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

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

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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.

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.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.

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

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’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.

DAB Enhancer for ampliying DAB stains in IHC staining, 60ml
NB308 60 ml
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DAB Enhancer for ampliying DAB stains in IHC staining, 30ml
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SensiTek HRP Anti-Mouse (DAB) Staining System
AEA080 70 Slides
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AEM080 70 Slides
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UltraTek HRP Anti-Mouse (DAB) Staining System
AKA080 70 Slides
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UltraTek HRP Anti-Rabbit (DAB) Staining System
AKC080 70 Slides
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UltraTek HRP Anti-Polyvalent (DAB) Staining System
AMF080 70 Slides
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Black-DAB Substrate/Chromogen System for IHC-HRP staining (stable), 70ml NEW
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Fmoc-Dab-OH
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B-2300.0001 1.0g
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Description: Sum Formula: C19H20N2O4; CAS# [161420-87-7]

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Description: Sum Formula: C19H20N2O4; CAS# [161420-87-7]

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Description: Sum Formula: C9H18N2O4; CAS# [25691-37-6]

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Description: Sum Formula: C9H18N2O4; CAS# [25691-37-6]

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Description: Sum Formula: C9H18N2O4; CAS# [25691-37-6]

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Description: Sum Formula: C12H16N2O4; CAS# [62234-40-6]

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Description: Sum Formula: C12H16N2O4; CAS# [62234-40-6]

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Description: Sum Formula: C12H16N2O4; CAS# [62234-40-6]

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Description: DL-Dab.2HCl

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Description: Sum Formula: C4H10N2O2; CAS# [1883-09-6]

H-Dab-OH
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EUR 225
Description: Sum Formula: C4H10N2O2; CAS# [1883-09-6]

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Description: Sum Formula: C4H10N2O2; CAS# [1883-09-6]

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EUR 297
Description: Sum Formula: C23H24N2O6; CAS# [204316-32-5]

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EUR 1106
Description: Sum Formula: C23H24N2O6; CAS# [204316-32-5]

Fmoc-Dab(Z)-OH
B-3250.0001 1.0g
EUR 261
Description: Sum Formula: C27H26N2O6; CAS# [252049-08-4]

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EUR 925
Description: Sum Formula: C27H26N2O6; CAS# [252049-08-4]

Fmoc-Dab(ivDde)-OH
B-4065.0001 1.0g
EUR 297
Description: Sum Formula: C32H38N2O6; CAS# [607366-21-2]

Fmoc-Dab(ivDde)-OH
B-4065.0005 5.0g
EUR 1093
Description: Sum Formula: C32H38N2O6; CAS# [607366-21-2]

Fmoc-Dab(Boc)-OH
B-1800.0001 1.0g
EUR 200
Description: Sum Formula: C24H28N2O6; CAS# [125238-99-5]

Fmoc-Dab(Boc)-OH
B-1800.0005 5.0g
EUR 683
Description: Sum Formula: C24H28N2O6; CAS# [125238-99-5]

Fmoc-Dab(Fmoc)-OH
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EUR 236
Description: Sum Formula: C34H30N2O6; CAS# [201473-83-8]

Fmoc-Dab(Fmoc)-OH
B-2270.0005 5.0g
EUR 866
Description: Sum Formula: C34H30N2O6; CAS# [201473-83-8]

Fmoc-D-Dab-OH
B-2365.0001 1.0g
EUR 418
Description: Sum Formula: C19H20N2O4; CAS# [201484-12-0]

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