Journal of Pain Management and Therapy

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Perspective - Journal of Pain Management and Therapy (2023) Volume 7, Issue 5

Epigenetic Alterations in Parkinson's Disease: Unraveling the Genetic Mysteries

John Allam*

Department of Pediatrics, Columbia University Medical Center, New York, US

*Corresponding Author:
John Allam
Department of Pediatrics
Columbia University Medical Center
New York, US
E-mail:Jnwestien09@unav.sp

Received:26-Aug-2023,Manuscript No. AAPMT-23-113473; Editor assigned: 29-Aug-2023, PreQC No. AAPMT-23-113473(PQ); Reviewed:12-Sept-2023, QC No. AAPMT-23-113473; Revised:18-Sept-2023, Manuscript No. AAPMT-23-113473(R); Published:25-Sept-2023, DOI: 10.35841/aapmt- 7.5.166

Citation: Allam J. Epigenetic alterations in Parkinson’s disease: Unraveling the genetic mysteries. J Pain Manage Ther. 2023;7(5):166

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Abstract

Parkinson's Disease (PD) is a complex neurodegenerative disorder with multifaceted etiology, and recent research has unveiled the significant role of epigenetic alterations in its pathogenesis. This article explores the emerging field of epigenetics in PD, shedding light on the epigenetic modifications, their potential mechanisms, and their implications for disease management.

Keywords

Parkinson's Disease, epigenetic alterations, DNA methylation, histone modifications, therapeutic targets.

Introduction

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms like cognitive impairment and mood disorders. While the exact cause of PD remains elusive, genetics plays a significant role in its development. However, recent research has uncovered the critical role of epigenetic alterations in the pathogenesis of PD, providing a new perspective on this debilitating disease[1].

 

Epigenetic alterations in Parkinson's disease

DNA methylation: DNA methylation is a fundamental epigenetic modification involving the addition of a methyl group to the DNA molecule, primarily at cytosine residues in CpG dinucleotides. In PD, aberrant DNA methylation patterns have been observed in various genes associated with dopaminergic signaling and neuroinflammation. For instance, the promoter regions of key genes like SNCA (encoding α-synuclein) and PINK1 (encoding a mitochondrial protein) exhibit hypermethylation, leading to reduced gene expression. These epigenetic changes can disrupt crucial cellular processes, including protein aggregation and mitochondrial function, contributing to PD pathogenesis[2].

Histone modifications: Histones are proteins that package and organize DNA into chromatin, and their modifications can influence gene expression. In PD, alterations in histone acetylation and methylation have been identified in genes related to dopamine regulation and oxidative stress. Histone deacetylase inhibitors (HDACi) have shown promise in preclinical studies as potential therapeutic agents by modulating histone acetylation levels and restoring gene expression patterns. HDACi can potentially ameliorate neuroinflammation and improve motor symptoms in PD patients[3].

Non-Coding RNAs: Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as essential regulators of gene expression in PD. Dysregulated miRNAs can target genes involved in dopaminergic neuron function and survival. For example, miR-133b, which is downregulated in PD, controls the expression of genes like TH (tyrosine hydroxylase) and α-synuclein. Manipulating these miRNAs could offer potential therapeutic avenues for PD. Additionally, lncRNAs like HOTAIR have been implicated in PD by influencing the expression of genes associated with mitochondrial dysfunction and oxidative stress[4].

Environmental factors and epigenetics: Environmental factors, such as exposure to pesticides and heavy metals, have been linked to an increased risk of developing PD. These environmental toxins can induce epigenetic modifications, further exacerbating the disease. For example, exposure to pesticides like paraquat and rotenone can lead to DNA methylation changes in dopaminergic neurons, affecting their function and survival. Understanding how environmental factors interact with epigenetic alterations in PD is crucial for developing preventive strategies.

Therapeutic implications: The identification of specific epigenetic alterations in PD opens up exciting possibilities for therapeutic intervention. Several compounds that target epigenetic enzymes, such as DNA methyltransferases and histone deacetylases, are being explored as potential PD treatments. These epigenetic-modifying drugs aim to restore normal gene expression patterns, mitigate neuroinflammation, and protect dopaminergic neurons. Clinical trials are ongoing to evaluate the safety and efficacy of these compounds in PD patients[5].

Conclusion

Epigenetic alterations are increasingly recognized as critical contributors to the pathogenesis of Parkinson's Disease. DNA methylation, histone modifications, non-coding RNAs, and environmental factors all play pivotal roles in shaping the epigenetic landscape in PD. Understanding these epigenetic mechanisms not only enhances our knowledge of PD's etiology but also provides new avenues for therapeutic development. Targeting epigenetic modifications holds promise for slowing disease progression and improving the quality of life for PD patients. As research in this field continues to advance, we may witness breakthroughs that bring us closer to effective treatments and, eventually, a cure for this devastating neurodegenerative disorder.

References

  1. Takeda A, Mallory M, Sundsmo M, et al.Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.Am J Pathol. 1998;152(2):367.

    2. Indexed at, Google Scholar

  2. Burn DJ.Cortical Lewy body disease and Parkinson's disease dementia.Curr Opin Neurol. 2006;19(6):572-9.

    3. Indexed at, Google Scholar, Cross Ref

  3. Jowaed A, Schmitt I, Kaut O, et al.Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains.J Neurosci. 2010;30(18):6355-9.

    4. Indexed at, Google Scholar, Cross Ref

  4. Hernandez DG, Nalls MA, Gibbs JR, et al.Distinct DNA methylation changes highly correlated with chronological age in the human brain.Human Mol Gene. 2011;20(6):1164-72.

    5. Indexed at, Google Scholar, Cross Ref

  5. Wilson AS, Power BE, Molloy PL.DNA hypomethylation and human diseases.Biochem. Biophys.. 2007;1775(1):138-62.

    6. Indexed at, Google Scholar, Cross Ref

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