RT Journal Article
T1 Elevated serum levels of Acid sphingomyelinase in female patients with episodic and chronic migraine
A1 Ouro Villasante, Alberto
A1 Castro Mosquera, Mónica
A1 Rodríguez Arrizabalaga, Mariña
A1 Debasa Mouce, Manuel
A1 Custodia, Antía
A1 Aramburu Núñez, Marta
A1 Romaus-Sanjurjo, Daniel
A1 Casas, Josefina
A1 Lema Gesto, María Isabel
A1 Castillo, José
A1 Leira Muiño, Rogelio
A1 Sobrino Moreiras, Tomás
K1 Acid sphingomyelinase
K1 Endothelial dysfunction
K1 Inflammation
K1 Migraine
K1 Oxidative stress
K1 Serum
K1 Sphingomyelin
K1 Vascular
AB Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide. Its activity has been associated with several molecular processes involved in migraine. Therefore, this cross-sectional study aims to study the potential role of aSMase in patients with episodic and chronic migraine. In this cross-sectional pilot study, serum samples from female healthy controls (n = 23), episodic migraine (EM) patients (n = 31), and chronic migraine (CM) patients (n = 28) were studied. The total serum levels of aSMase were determined by ELISA. In addition, the serum levels of sphingomyelin (SM), dihydro-sphingomyelin (dhSM), ceramide (Cer), and dihydro-ceramide (dhCer) were determined by mass spectrometry as biomarkers involved in the main molecular pathways associated with aSMase. aSMase serum levels were found significantly elevated in both EM (3.62 ± 1.25 ng/mL) and CM (3.07 ± 0.95 ng/mL) compared with controls (1.58 ± 0.72 ng/mL) (p < 0.0001). ROC analysis showed an area under the curve (AUC) of 0.94 (95% CI: 0.89–0.99, p < 0.0001) and 0.90 (95% CI: 0.81–0.99, p < 0.0001) for EM and CM compared to controls, respectively. Regarding other biomarkers associated with aSMase’s pathways, total SM serum levels were significantly decreased in both EM (173,534 ± 39,096 pmol/mL, p < 0.01) and CM (158,459 ± 40,010 pmol/mL, p < 0.0001) compared to the control subjects (219,721 ± 36,950 pmol/mL). Elevated serum levels of aSMase were found in EM and CM patients compared to the control subjects. The decreased SM levels found in both EM and CM indicate that aSMase activity plays a role in migraine. Therefore, aSMase may constitute a new therapeutic target in migraine that should be further investigated.
PB MDPI
YR 2025
FD 2025-01-29
LK https://hdl.handle.net/10347/43736
UL https://hdl.handle.net/10347/43736
LA eng
NO Ouro, A.; Castro-Mosquera, M.; Rodríguez-Arrizabalaga, M.; Debasa-Mouce, M.; Custodia, A.; Aramburu-Núñez, M.; Romaus-Sanjurjo, D.; Casas, J.; Lema, I.; Castillo, J.; et al. Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine. Antioxidants 2025, 14, 159. https://doi.org/10.3390/antiox14020159
NO This study was partially supported by grants from the Xunta de Galicia (IN607A2022/07), Instituto de Salud Carlos III (ISCIII) (PI22/00938), Interregional POCTEP 2021-2027: Programa de TransfireSaúde 2024 (Project NeurAlemab), and CIBERNED (CB22/05/00067), and Ministerio de Ciencia e Innovación (PDC2022-134000-I00). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No. 101066444). Furthermore, this study was also supported by grants from the INTERREG Atlantic Area (EAPA_791/2018_NEUROATLANTIC project), INTER-REG V A España Portugal (POCTEP) (0624_2IQBIONEURO_6_E), and the European Regional Development Fund (ERDF). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the PhD manuscript.
DS Minerva
RD 24 abr 2026