Mogavero Maria P, Fowowe Mojibola, Sanni Akeem, Goli Mona, Lanza Giuseppe, L'Episcopo Francesca, Ferini-Strambi Luigi, Mechref Yehia, Ferri Raffaele
Vita-Salute San Raffaele University, Milan, Italy.
San Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, Milan, Italy.
Mov Disord. 2025 Jun;40(6):1148-1159. doi: 10.1002/mds.30125. Epub 2025 Jan 30.
Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by an urge to move the legs, often with unpleasant sensations, particularly during rest. Current treatments include iron supplementation, dopamine agonists, and opioids, but new therapeutic approaches are needed. The dysfunction of the A11 nucleus, which modulates dopaminergic transmission to the spinal cord, is thought to play a role in RLS pathophysiology. Calcitonin gene-related peptide (CGRP), which is involved in pain modulation, may interact with A11 pathways, suggesting a role in RLS.
This study aimed to assess the involvement of CGRP in RLS by determining if CGRP-related proteins are overexpressed in RLS patients.
A cross-sectional study was conducted with 17 drug-free RLS patients (mean age 55.8 years) and 17 age- and gender-matched controls. Serum samples were analyzed using liquid chromatography-parallel reaction monitoring-tandem mass spectrometry (LC-PRM-MS/MS) to identify and quantify CGRP-related proteins. Principal component analysis (PCA) was used to differentiate between groups.
PCA showed clear differentiation between RLS and control groups. Among 13 identified CGRP-related proteins, 10 were dysregulated in RLS patients: 8 were upregulated, and 2 were downregulated, among them notable proteins such as S100A12, ADM, SRSF6, and ADM2.
This study indicates the significant involvement of CGRP and related proteins in RLS. This suggests these proteins may play roles in various aspects of the disorder. Further research is required to validate these findings and explore their clinical implications, including development of new treatment options that specifically address CGRP pathways. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
不宁腿综合征（RLS）是一种常见的感觉运动障碍，其特征是腿部有活动冲动，常伴有不适感，尤其是在休息时。目前的治疗方法包括补充铁剂、多巴胺激动剂和阿片类药物，但需要新的治疗方法。调节多巴胺能向脊髓传递的A11核功能障碍被认为在RLS病理生理过程中起作用。参与疼痛调节的降钙素基因相关肽（CGRP）可能与A11通路相互作用，提示其在RLS中发挥作用。
本研究旨在通过确定CGRP相关蛋白在RLS患者中是否过度表达来评估CGRP在RLS中的作用。
对17例未服用药物的RLS患者（平均年龄55.8岁）和17例年龄及性别匹配的对照者进行了横断面研究。使用液相色谱-平行反应监测-串联质谱（LC-PRM-MS/MS）分析血清样本，以鉴定和定量CGRP相关蛋白。主成分分析（PCA）用于区分两组。
PCA显示RLS组和对照组之间有明显差异。在鉴定出的13种CGRP相关蛋白中，10种在RLS患者中表达失调：8种上调，2种下调，其中包括S100A12、ADM、SRSF6和ADM2等显著蛋白。
本研究表明CGRP及其相关蛋白在RLS中显著参与。这表明这些蛋白可能在该疾病的各个方面发挥作用。需要进一步研究来验证这些发现并探索其临床意义，包括开发专门针对CGRP通路的新治疗方案。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
