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Publicação
Metabolomic signature of circulatory body fluids of individuals with Parkinson’s disease
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Orientador(es)
Resumo(s)
Parkinson’s disease (PD) is the second most common neurodegenerative disease associated with
aging, characterized by progressive loss of dopaminergic neurons in the substantia nigra. PD affects
about 10 million people globally, primarily those over 60 years. Current diagnostic methods are solely
symptomatic, when disease is in advanced stage with substantial neuronal loss. There’s an urgent need
for early and accurate diagnosis of PD to enable timely treatment and improve the patient’s quality of
life. This study aimed to develop an analytical workflow to identify potential biomarkers for PD across
different stages using untargeted metabolomics.
Metabolomic profiling was performed on 16 plasma samples from idiopathic PD patients and 9
control samples, aged 47 to 83, categorized by Hoehn and Yahr (HY) stages. Ultra-performance liquid
chromatography coupled with high-resolution mass spectrometry (UPLC-ESI-HR-MS) was used to
analyze the samples. The workflow optimization included solvent extraction, mobile phase selection,
and chromatographic separation, enhancing metabolite detection sensitivity. Multivariate statistical
methods (PCA and PLS-DA) enabled differentiation between disease stages and control groups, with
high R² and Q² values indicating strong predictive power.
From the PLS-DA analysis, 400 variables of importance (VIP) were identified, leading to the
annotation of 46 putative biomarkers. The main findings revealed significant alterations in lipid, bile
acid, and steroid metabolism, alongside amino acid biosynthesis and oxidative stress.
Glycerophospholipids emerged as a highly enriched pathway, with increased membrane degradation
and remodeling. Dysregulated metabolites such as lysophosphatidylcholines, oxidized fatty acids, and
sphingomyelins indicate membrane degradation and neuroinflammation. The presence of
glycodeoxycholic acid and reduced neuroprotective steroids highlights the role of the gut-brain axis and
neuronal vulnerability in PD progression.
In summary, this study provides workflow for metabolite extraction and analysis, identifying
potential biomarkers for PD staging. These biomarkers offer promising targets for early diagnosis and
therapeutic intervention, potentially improving outcomes for PD patients.
Descrição
Tese de mestrado, Química (Química), 2025, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Doença de Parkinson metabolómica cromatografia liquída espectrometria de massa biomarcador Teses de mestrado - 2025