Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis
Maria P. Mogavero,
Michele Salemi,
Giuseppe Lanza,
Antonio Rinaldi,
Giovanna Marchese,
Maria Ravo,
Maria Grazia Salluzzo,
Amedeo Antoci,
Lourdes M. DelRosso,
Oliviero Bruni,
Luigi Ferini-Strambi,
Raffaele Ferri
Affiliations
Maria P. Mogavero
Vita-Salute San Raffaele University, 20132 Milan, Italy; San Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, 20127 Milan, Italy
Michele Salemi
Oasi Research Institute-IRCCS, 94018 Troina, Italy
Giuseppe Lanza
Oasi Research Institute-IRCCS, 94018 Troina, Italy; University of Catania, Department of Surgery and Medical-Surgical Specialties, 95123 Catania, Italy
Antonio Rinaldi
Genomix4Life Srl, 84081 Baronissi, Italy; Genome Research Center for Health-CRGS, 84081 Baronissi, Italy
Giovanna Marchese
Genomix4Life Srl, 84081 Baronissi, Italy; Genome Research Center for Health-CRGS, 84081 Baronissi, Italy
Maria Ravo
Genomix4Life Srl, 84081 Baronissi, Italy; Genome Research Center for Health-CRGS, 84081 Baronissi, Italy
Maria Grazia Salluzzo
Oasi Research Institute-IRCCS, 94018 Troina, Italy
Amedeo Antoci
Oasi Research Institute-IRCCS, 94018 Troina, Italy
Lourdes M. DelRosso
University of California San Francisco-Fresno, Fresno, CA 93721, USA
Oliviero Bruni
Sapienza University of Rome, Developmental and Social Psychology, 00185 Rome, Italy
Luigi Ferini-Strambi
Vita-Salute San Raffaele University, 20132 Milan, Italy; San Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, 20127 Milan, Italy
Raffaele Ferri
Oasi Research Institute-IRCCS, 94018 Troina, Italy; Corresponding author
Summary: The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms. Genetic predisposition plays a key role in RLS and evidence indicates its inflammatory nature; the high involvement of mainly neurotropic viruses and the TORCH complex might trigger inflammatory/immune reactions in genetically predisposed subjects and activate a series of biological pathways—especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer of activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, and ferroptosis—involved in neurotransmitter mechanisms, synaptic plasticity, axon guidance, neurodegeneration, carcinogenesis, and metabolism.
