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

Abstract

\n\nNeurodegenerative disorders are one of the major health problems\nin Western countries. Genetic and epigenetic mechanisms play crucial roles in the\norigin and progression of these disorders. DNA methylation is the most widely studied epigenetic\nmark and is an important regulator of gene expression.\n\n\n\nLittle is known about the influence of bioactive dietary components on epigenetic\nmechanisms in neurodegenerative diseases. In this study, we investigated the effects\nof E-PodoFavalin-15999 (AtreMorine®), a bioproduct with potent neuroprotective and dopamine\nenhancing capabilities, on DNA methylation patterns in Alzheimer’s (AD) and\nParkinson’s Disease (PD). We also aimed to assess, in patients with PD, the effects that\ngenetic variation across candidate pharmacogenes may have on dopamine synthesis and\nrelease in response to treatment with AtreMorine.\n\n\n\nWe analyzed global DNA methylation and de novo DNA methyltransferase\n(DNMT) expression in a transgenic (3xTg) mouse model of AD, and further examined\nglobal DNA methylation in blood samples from patients with PD.\n\n\n\nAtreMorine treatment increased global DNA methylation in 3xTg mice and in\npatients with Parkinson´s disease, and produced high DNMT3a expression in AD mice.\nWe observed varied responses to AtreMorine across the following pharmacogenetic genophenotypes\nanalyzed, cytochrome P450 oxidases (CYP2D6, CYP2C19, CYP2C9,\nCYP3A4, CYP3A5, CYP1A2), human arylamine N-acetyltransferase 2 (NAT2), the vitamin\nK epoxide reductase complex subunit 1 (VKORC1), ATP-binding cassette subfamily B\nmember 1 (ABCB1), and solute carrier organic anion transporter family member 1B1\n(SLCOB1).\n\n\n\n Our results suggest that AtreMorine regulates DNA methylation in neurodegenerative\ndisorders and may constitute a new therapeutic option for the treatment of\nthese pathologies.\n