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Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

AtreMorine Treatment Regulates DNA Methylation in Neurodegenerative Disorders: Epigenetic and Pharmacogenetic Studies

Author(s): Olaia Martínez-Iglesias*, Vinogran Naidoo, Juan Carlos Carril, Iván Carrera, Lola Corzo, Susana Rodriguez, Ramón Alejo, Natalia Cacabelos and Ramón Cacabelos

Volume 17 , Issue 3 , 2020

Page: [159 - 171] Pages: 13

DOI: 10.2174/1875692117999201231152800

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Abstract

Background: Neurodegenerative disorders are one of the major health problems in Western countries. Genetic and epigenetic mechanisms play crucial roles in the origin and progression of these disorders. DNA methylation is the most widely studied epigenetic mark and is an important regulator of gene expression.

Objective: Little is known about the influence of bioactive dietary components on epigenetic mechanisms in neurodegenerative diseases. In this study, we investigated the effects of E-PodoFavalin-15999 (AtreMorine®), a bioproduct with potent neuroprotective and dopamine enhancing capabilities, on DNA methylation patterns in Alzheimer’s (AD) and Parkinson’s Disease (PD). We also aimed to assess, in patients with PD, the effects that genetic variation across candidate pharmacogenes may have on dopamine synthesis and release in response to treatment with AtreMorine.

Methods: We analyzed global DNA methylation and de novo DNA methyltransferase (DNMT) expression in a transgenic (3xTg) mouse model of AD, and further examined global DNA methylation in blood samples from patients with PD.

Results: AtreMorine treatment increased global DNA methylation in 3xTg mice and in patients with Parkinson´s disease, and produced high DNMT3a expression in AD mice. We observed varied responses to AtreMorine across the following pharmacogenetic genophenotypes analyzed, cytochrome P450 oxidases (CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, CYP1A2), human arylamine N-acetyltransferase 2 (NAT2), the vitamin K epoxide reductase complex subunit 1 (VKORC1), ATP-binding cassette subfamily B member 1 (ABCB1), and solute carrier organic anion transporter family member 1B1 (SLCOB1).

Conclusion: Our results suggest that AtreMorine regulates DNA methylation in neurodegenerative disorders and may constitute a new therapeutic option for the treatment of these pathologies.

Keywords: Neurodegeneration, Alzheimer´s disease, Parkinson´s disease, DNA methylation, DNMTs, Atre- Morine.

Graphical Abstract

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