Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions

Abstract Spinal Muscular Atrophy (SMA) is a neuromuscular disorder precipitated by mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene. Although the SMN2 gene partially compensates for SMN1 functional deficiency, its expression is regulated by complex epigenetic and environmental facto...

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Main Authors: Haoran Li, Bo Yu, Ye yuan, Nannan Chen, Jimeng Wu, Zhiqing Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Orphanet Journal of Rare Diseases
Subjects:
Online Access:https://doi.org/10.1186/s13023-025-03857-3
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author Haoran Li
Bo Yu
Ye yuan
Nannan Chen
Jimeng Wu
Zhiqing Zhang
author_facet Haoran Li
Bo Yu
Ye yuan
Nannan Chen
Jimeng Wu
Zhiqing Zhang
author_sort Haoran Li
collection DOAJ
description Abstract Spinal Muscular Atrophy (SMA) is a neuromuscular disorder precipitated by mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene. Although the SMN2 gene partially compensates for SMN1 functional deficiency, its expression is regulated by complex epigenetic and environmental factors. This review comprehensively elucidates the regulatory mechanisms through which epigenetic modifications-encompassing DNA methylation, histone modifications, and non-coding RNAs-modulate SMN2 gene expression and impact SMA pathogenesis and progression. We also briefly discuss how these epigenetic mechanisms may interact with selected environmental factors in modifying disease outcomes. Emerging evidence suggests that these epigenetic factors and environmental exposures interact synergistically to influence disease trajectory and may account for the heterogeneity observed in SMA clinical manifestations. These insights have given rise to novel therapeutic strategies, including pharmacological interventions targeting epigenetic pathways and optimized management of environmental factors. Integrating multi-omics analyses holds promise for advancing personalized precision medicine approaches for SMA and potentially improving patient outcomes.
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institution DOAJ
issn 1750-1172
language English
publishDate 2025-07-01
publisher BMC
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series Orphanet Journal of Rare Diseases
spelling doaj-art-03f635a36df24e1fa3e4868a72c5407d2025-08-20T03:06:05ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-0120111810.1186/s13023-025-03857-3Epigenetic regulation in spinal muscular atrophy: emerging areas and future directionsHaoran Li0Bo Yu1Ye yuan2Nannan Chen3Jimeng Wu4Zhiqing Zhang5Department of Pharmacy, The Second Hospital of Hebei Medical UniversityDepartment of Pediatrics, The Second Hospital of Hebei Medical UniversityDepartment of Pharmacy, The Second Hospital of Hebei Medical UniversityDepartment of Pharmacy, The Second Hospital of Hebei Medical UniversitySchool of Basic Medicine, Chengde Medical CollegeDepartment of Pharmacy, The Second Hospital of Hebei Medical UniversityAbstract Spinal Muscular Atrophy (SMA) is a neuromuscular disorder precipitated by mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene. Although the SMN2 gene partially compensates for SMN1 functional deficiency, its expression is regulated by complex epigenetic and environmental factors. This review comprehensively elucidates the regulatory mechanisms through which epigenetic modifications-encompassing DNA methylation, histone modifications, and non-coding RNAs-modulate SMN2 gene expression and impact SMA pathogenesis and progression. We also briefly discuss how these epigenetic mechanisms may interact with selected environmental factors in modifying disease outcomes. Emerging evidence suggests that these epigenetic factors and environmental exposures interact synergistically to influence disease trajectory and may account for the heterogeneity observed in SMA clinical manifestations. These insights have given rise to novel therapeutic strategies, including pharmacological interventions targeting epigenetic pathways and optimized management of environmental factors. Integrating multi-omics analyses holds promise for advancing personalized precision medicine approaches for SMA and potentially improving patient outcomes.https://doi.org/10.1186/s13023-025-03857-3Spinal muscular atrophyEpigeneticsEnvironmental factorsSMN2 gene
spellingShingle Haoran Li
Bo Yu
Ye yuan
Nannan Chen
Jimeng Wu
Zhiqing Zhang
Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
Orphanet Journal of Rare Diseases
Spinal muscular atrophy
Epigenetics
Environmental factors
SMN2 gene
title Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
title_full Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
title_fullStr Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
title_full_unstemmed Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
title_short Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions
title_sort epigenetic regulation in spinal muscular atrophy emerging areas and future directions
topic Spinal muscular atrophy
Epigenetics
Environmental factors
SMN2 gene
url https://doi.org/10.1186/s13023-025-03857-3
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AT boyu epigeneticregulationinspinalmuscularatrophyemergingareasandfuturedirections
AT yeyuan epigeneticregulationinspinalmuscularatrophyemergingareasandfuturedirections
AT nannanchen epigeneticregulationinspinalmuscularatrophyemergingareasandfuturedirections
AT jimengwu epigeneticregulationinspinalmuscularatrophyemergingareasandfuturedirections
AT zhiqingzhang epigeneticregulationinspinalmuscularatrophyemergingareasandfuturedirections