Title:AtreMorine Treatment Regulates DNA Methylation in Neurodegenerative Disorders: Epigenetic and Pharmacogenetic Studies
Volume: 17
Issue: 3
Author(s): Olaia Martínez-Iglesias*, Vinogran Naidoo, Juan Carlos Carril, Iván Carrera, Lola Corzo, Susana Rodriguez, Ramón Alejo, Natalia Cacabelos and Ramón Cacabelos
Affiliation:
- EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, Bergondo 15165 Corunna,Spain
Keywords:
Neurodegeneration, Alzheimer´s disease, Parkinson´s disease, DNA methylation, DNMTs, Atre-
Morine.
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.