Epigenetic Alterations in Hereditary Neurological Disorders

Epigenetic Alterations in Hereditary Neurological Disorders
Ali Rezaei,¹ Shirin Farivar,^2,*
1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
2. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
Introduction: The genetic mutations that cause hereditary neurological disorders (HNDs) including Huntington’s disease (HD), spinocerebellar ataxias (SCAs), and fragile X syndrome (FXS) show increasing evidence of epigenetic regulation. The three main epigenetic mechanisms of DNA methylation, histone modification, and non-coding RNA regulation control both neurodevelopment and neuronal plasticity. The disruption of these processes leads to disease initiation and determines how diseases progress and how their symptoms manifest differently in patients. The paper reviews existing research about hereditary neurological condition epigenetic changes which appeared in scientific publications starting from 2020.
Methods: The research used peer-reviewed articles from 2020 until present for its targeted literature review. The research included studies which analyzed hereditary neurological disorders through DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs. The review focused on understanding mechanisms while exploring potential biomarkers and therapeutic applications.
Results: Results 1. DNA Methylation in Disease Pathogenesis Multiple HNDs show evidence of abnormal DNA methylation patterns in their molecular profiles. The progression of HD becomes worse because of gene expression changes that occur through DNA methylation modifications which affect survival mechanisms and synaptic function. The FMR1 promoter in FXS develops hypermethylation which blocks gene expression and disrupts neuronal communication. 2. Histone Modifications and Chromatin Remodeling Neurodegenerative diseases show histone acetylation and methylation as their primary mechanisms of progression. The transcriptional dysregulation of neuronal genes in SCAs occurs because of histone hypoacetylation. Polyglutamine expansion disorders create chromatin remodeling problems which result in damaged DNA repair mechanisms and make neurons more susceptible to damage. 3. Role of Non-coding RNAs The gene expression networks that control HNDs receive their regulatory signals from microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Research shows that Huntington’s disease and ataxia patients develop synaptic plasticity problems and neuronal apoptosis because of miRNA dysregulation. The expression patterns of miRNAs in FXS patients affect the development of synaptic connections. 4. Epigenetic Biomarkers for Diagnosis and Prognosis Scientists are currently investigating epigenetic patterns for their potential use as diagnostic markers. Blood-based methylation profiling can identify HD progression stages and predict ataxia severity. The development of these biomarkers enables doctors to detect diseases at an early stage while creating individualized treatment plans. 5. Therapeutic Implications Preclinical studies demonstrate that histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) modulators represent promising therapeutic approaches for epigenetic treatment. Research on HDAC inhibitors in animal models demonstrates their ability to enhance neuronal survival and improve motor function. The use of epigenetic regulators as disease-modifying treatments faces two major obstacles because of their potential safety risks and limited specificity.
Conclusion: The fundamental regulatory mechanism of hereditary neurological disorders exists through epigenetic changes which affect disease timing, progression, and individual disease expression. Research on DNA methylation, histone modifications, and non-coding RNAs reveals both disease mechanisms and therapeutic possibilities. The implementation of epigenetic research in clinical settings will improve early disease detection and create new therapeutic options. Research should concentrate on conducting long-term studies and clinical trials to prove the effectiveness of epigenetic biomarkers and treatments.
Keywords: Epigenetics; DNA methylation; Histone modification; Non-coding RNA