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.
Highlights
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disorder, involving several motor functions, vegetative, behavioural and cognitive impairments [1,2,3]
A limited set of lipids have been characterized in skin fibroblasts of parkin-mutant patients by matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS) [28], whereas a more extensive, but still not exhaustive, lipidome characterization by hydrophilic interaction liquid chromatography (HILIC) ESI FTMS has been undertaken in our laboratory [32]
The phospholipidome of FB obtained from skin biopsies of five patients with Parkinson’s disease at different progression stages (Hoehn and Yahr scale) was compared to a control
Summary
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disorder, involving several motor functions, vegetative, behavioural and cognitive impairments [1,2,3]. These findings, preliminary, suggest that the phospholipidome of human dermal FB represents a source of potential biomarkers for early diagnosis of Parkinson’s disease. A limited set of lipids have been characterized in skin fibroblasts of parkin-mutant patients by MALDI MS [28], whereas a more extensive, but still not exhaustive, lipidome characterization by HILIC ESI FTMS has been undertaken in our laboratory [32] These recently reported data along with those here described lead to the identification of 360 phospholipids.
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