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Int J Mol Sci. 2019 Jul 7;20(13). pii: E3341. doi: 10.3390/ijms20133341.

Searching for Potential Lipid Biomarkers of Parkinson's Disease in Parkin-Mutant Human Skin Fibroblasts by HILIC-ESI-MS/MS: Preliminary Findings.

Author information

1
Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari, Italy. cosimadamiana.calvano@uniba.it.
2
Centro Interdipartimentale SMART, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari, Italy. cosimadamiana.calvano@uniba.it.
3
Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari, Italy.
4
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", 70100 Bari, Italy. annamaria.sardanelli@uniba.it.
5
Department of Medicine, Campus Bio-Medico University of Rome, 00128 Roma, Italy. annamaria.sardanelli@uniba.it.
6
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", 70100 Bari, Italy.
7
Centro Interdipartimentale SMART, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari, Italy.
8
Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy.

Abstract

Early diagnosis of neural changes causing cerebral impairment is critical for proposing preventive therapies for Parkinson's disease (PD). Biomarkers currently available cannot be informative of PD onset since they are characterized by analysing post-mortem tissues from patients with severe degeneration of the substantia nigra. Skin fibroblasts (SF) are now recognized as a useful model of primary human cells, capable of reflecting the chronological and biological aging of the subjects. Here a lipidomic study of easily accessible primary SF is presented, based on hydrophilic interaction liquid chromatography coupled to electrospray ionization and mass spectrometry (HILIC/ESI-MS). Phospholipids (PL) from dermal fibroblasts of five PD patients with different parkin mutations and healthy control SF were characterized by single and tandem MS measurements using a hybrid quadrupole-Orbitrap and a linear ion trap mass analysers. The proposed approach enabled the identification of more than 360 PL. Univariate statistical analyses highlight abnormality of PL metabolism in the PD group, suggesting down- or up-regulation of certain species according to the extent of disease progression. These findings, although preliminary, suggest that the phospholipidome of human SF represents a source of potential biomarkers for the early diagnosis of PD. The dysregulation of ethanolamine plasmalogens in the circulatory system, especially those containing polyunsaturated fatty acids (PUFA), might be likely associated with neurodegeneration.

KEYWORDS:

HILIC-tandem MS; Parkinson’s disease; biomarker; human skin fibroblasts; lipidomics

PMID:
31284683
PMCID:
PMC6650793
DOI:
10.3390/ijms20133341
[Indexed for MEDLINE]
Free PMC Article

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