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Comparative Peripheral Blood Transcriptomic Profiles in Parkinson's Disease and Restless Legs Syndrome: An
Maria P Mogavero1, Giovanna Marchese2,3, Giovanna M Ventola2
1Oasi Research Institute-IRCCS, 94018 Troina, Italy.
International Journal of Molecular Sciences
|August 13, 2026
Summary
Parkinson's disease (PD) and restless legs syndrome (RLS) show distinct peripheral blood gene expression patterns. Transcriptomics may reveal biological differences underlying RLS-like symptoms in PD patients.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Restless legs syndrome (RLS) symptoms are common in Parkinson's disease (PD).
- The biological basis for this overlap, whether shared or convergent, is unclear.
- Previous studies lack comparative transcriptomic analysis between RLS and PD.
Purpose of the Study:
- To explore differences in peripheral blood gene expression between patients with RLS and PD.
- To investigate potential shared or distinct biological pathways involved in RLS and PD.
Main Methods:
- Comparative analysis of peripheral blood mononuclear cell RNA-sequencing data.
- 17 drug-free RLS patients and 60 PD patients (mostly on dopaminergic treatment) were analyzed.
- Differential gene expression and pathway analyses were performed.
Main Results:
- Significant transcriptomic separation was observed between PD and RLS groups.
- PD showed higher expression of genes related to dopamine metabolism, iron transport, oxidative stress, and inflammation.
- RLS showed higher expression of genes involved in iron/ferroptosis, GPCR signaling, synaptic modulation, and circadian pathways.
Conclusions:
- Peripheral blood transcriptomics can generate hypotheses regarding the biological heterogeneity of RLS-like symptoms in PD.
- Findings are hypothesis-generating due to limitations including treatment imbalance, cohort differences, and lack of healthy controls.
- Independent validation is required to confirm these transcriptomic differences.
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