Epigenetic Modulation in Parkinson's Disease and Potential Treatment Therapies

doi:10.1007/s11064-021-03334-w

Review

. 2021 Jul;46(7):1618-1626.

doi: 10.1007/s11064-021-03334-w. Epub 2021 Apr 26.

Epigenetic Modulation in Parkinson's Disease and Potential Treatment Therapies

Aaina Singh Rathore¹, Hareram Birla¹, Saumitra Sen Singh¹, Walia Zahra¹, Hagera Dilnashin¹, Richa Singh¹, Priyanka Kumari Keshri¹, Surya Pratap Singh²

Affiliations

¹ Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
² Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. suryasinghbhu16@gmail.com.

PMID: 33900517
DOI: 10.1007/s11064-021-03334-w

Review

Epigenetic Modulation in Parkinson's Disease and Potential Treatment Therapies

Aaina Singh Rathore et al. Neurochem Res. 2021 Jul.

. 2021 Jul;46(7):1618-1626.

doi: 10.1007/s11064-021-03334-w. Epub 2021 Apr 26.

Authors

Aaina Singh Rathore¹, Hareram Birla¹, Saumitra Sen Singh¹, Walia Zahra¹, Hagera Dilnashin¹, Richa Singh¹, Priyanka Kumari Keshri¹, Surya Pratap Singh²

Affiliations

¹ Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
² Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. suryasinghbhu16@gmail.com.

PMID: 33900517
DOI: 10.1007/s11064-021-03334-w

Abstract

In the recent past, huge emphasis has been given to the epigenetic alterations of the genes responsible for the cause of neurological disorders. Earlier, the scientists believed somatic changes and modifications in the genetic makeup of DNA to be the main cause of the neurodegenerative diseases. With the increase in understanding of the neural network and associated diseases, it was observed that alterations in the gene expression were not always originated by the change in the genetic sequence. For this reason, extensive research has been conducted to understand the role of epigenetics in the pathophysiology of several neurological disorders including Alzheimer's disease, Parkinson's disease and, Huntington's disease. In a healthy person, the epigenetic modifications play a crucial role in maintaining the homeostasis of a cell by either up-regulating or down-regulating the genes. Therefore, improved understanding of these modifications may provide better insight about the diseases and may serve as potential therapeutic targets for their treatment. The present review describes various epigenetic modifications involved in the pathology of Parkinson's Disease (PD) backed by multiple researches carried out to study the gene expression regulation related to the epigenetic alterations. Additionally, we will briefly go through the current scenario about the various treatment therapies including small molecules and multiple phytochemicals potent enough to reverse these alterations and the future directions for a better management of PD.

Keywords: Acetylation; Deacetylation; Epigenetic modulators; Methylation; Parkinson’s disease; RNA based gene regulation.

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[1] Shults CW (2006) Lewy bodies. Proc Natl Acad Sci USA 103(6):1661. https://doi.org/10.1073/pnas.0509567103 - DOI - PubMed

[2] Shults CW (2006) Lewy bodies. Proc Natl Acad Sci USA 103(6):1661. https://doi.org/10.1073/pnas.0509567103 - DOI - PubMed

[3] Wakabayashi K, Tanji K, Mori F, Takahashi H (2007) The Lewy body in Parkinson’s disease: molecules implicated in the formation and degradation of α-synuclein aggregates. Neuropathology 27(5):494–506. https://doi.org/10.1111/j.1440-1789.2007.00803.x - DOI - PubMed

[4] Wakabayashi K, Tanji K, Mori F, Takahashi H (2007) The Lewy body in Parkinson’s disease: molecules implicated in the formation and degradation of α-synuclein aggregates. Neuropathology 27(5):494–506. https://doi.org/10.1111/j.1440-1789.2007.00803.x - DOI - PubMed

[5] Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, Ikram MA, Ioannidis JPA, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB, International Parkinson's Disease Genomics Consortium (IPDGC); Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI); 23andMe; GenePD; NeuroGenetics Research Consortium (NGRC); Hussman Institute of Human Genomics (HIHG); Ashkenazi Jewish Dataset Investigator; Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE); North American Brain Expression Consortium (NABEC); United Kingdom Brain Expression Consortium (UKBEC); Greek Parkinson's Disease Consortium; Alzheimer Genetic Analysis Group (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics 46(9):989–993. https://doi.org/10.1038/ng.3043

[6] Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, Ikram MA, Ioannidis JPA, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB, International Parkinson's Disease Genomics Consortium (IPDGC); Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI); 23andMe; GenePD; NeuroGenetics Research Consortium (NGRC); Hussman Institute of Human Genomics (HIHG); Ashkenazi Jewish Dataset Investigator; Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE); North American Brain Expression Consortium (NABEC); United Kingdom Brain Expression Consortium (UKBEC); Greek Parkinson's Disease Consortium; Alzheimer Genetic Analysis Group (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics 46(9):989–993. https://doi.org/10.1038/ng.3043

[7] Santiago P (2012) Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. Sci World J 2012:846824. https://doi.org/10.1100/2012/846824 - DOI

[8] Santiago P (2012) Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. Sci World J 2012:846824. https://doi.org/10.1100/2012/846824 - DOI

[9] Hamza TH, Payami H (2010) The heritability of risk and age at onset of Parkinson’s disease after accounting for known genetic risk factors. J Hum Genet 55(4):241–243. https://doi.org/10.1038/jhg.2010.13 - DOI - PubMed - PMC

[10] Hamza TH, Payami H (2010) The heritability of risk and age at onset of Parkinson’s disease after accounting for known genetic risk factors. J Hum Genet 55(4):241–243. https://doi.org/10.1038/jhg.2010.13 - DOI - PubMed - PMC

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Epigenetic Modulation in Parkinson's Disease and Potential Treatment Therapies

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Epigenetic Modulation in Parkinson's Disease and Potential Treatment Therapies

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