MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1 beta), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS. We specifically focused on the single-nucleotide polymorphism Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene, known for its crucial role in CNS functioning. We assessed the levels of miR-142-3p and IL1 beta in cerebrospinal fluid (CSF) obtained from a cohort of 114 patients with MS upon diagnosis. By stratifying patients according to their genetic background, statistical correlations with clinical parameters were performed. Notably, in Met-carrier patients, we observed a decoupling of miR-142-3p levels from IL1 beta levels in the CSF, as well as from of disease severity (Expanded Disability Status Score, EDSS; Multiple Sclerosis Severity Score, MSSS; Age-Related Multiple Sclerosis Severity Score, ARMSS) and progression (Progression Index, PI). Our discovery of the interference between BDNF Val66Met polymorphism and the synaptotoxic IL1 beta-miR-142-3p axis, therefore hampering miR-142-3p action on MS course, provides valuable insights for further development of personalized medicine in the field.

Dolcetti, E., Musella, A., Balletta, S., Gilio, L., Bruno, A., Stampanoni Bassi, M., et al. (2024). Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25(10), 1-14 [10.3390/ijms25105253].

Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity

Dolcetti, Ettore;Musella, Alessandra;Balletta, Sara;Gilio, Luana;Stampanoni Bassi, Mario;Lauritano, Gianluca;Buttari, Fabio;Fresegna, Diego;Tartacca, Alice;Palmerio, Federica;Rovella, Valentina;Gambardella, Stefano;Giardina, Emiliano;Centonze, Diego;De Vito, Francesca
2024-05-11

Abstract

MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1 beta), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS. We specifically focused on the single-nucleotide polymorphism Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene, known for its crucial role in CNS functioning. We assessed the levels of miR-142-3p and IL1 beta in cerebrospinal fluid (CSF) obtained from a cohort of 114 patients with MS upon diagnosis. By stratifying patients according to their genetic background, statistical correlations with clinical parameters were performed. Notably, in Met-carrier patients, we observed a decoupling of miR-142-3p levels from IL1 beta levels in the CSF, as well as from of disease severity (Expanded Disability Status Score, EDSS; Multiple Sclerosis Severity Score, MSSS; Age-Related Multiple Sclerosis Severity Score, ARMSS) and progression (Progression Index, PI). Our discovery of the interference between BDNF Val66Met polymorphism and the synaptotoxic IL1 beta-miR-142-3p axis, therefore hampering miR-142-3p action on MS course, provides valuable insights for further development of personalized medicine in the field.
11-mag-2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26
Settore MEDS-12/A - Neurologia
English
biomarker
microRNA
neuroinflammation
proinflammatory cytokine
synapsis
synaptopathy
Dolcetti, E., Musella, A., Balletta, S., Gilio, L., Bruno, A., Stampanoni Bassi, M., et al. (2024). Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25(10), 1-14 [10.3390/ijms25105253].
Dolcetti, E; Musella, A; Balletta, S; Gilio, L; Bruno, A; Stampanoni Bassi, M; Lauritano, G; Buttari, F; Fresegna, D; Tartacca, A; Mariani, F; Palmeri...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/389860
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