Novel neurotrophic growth factor signaling pathway mediates changes in epigenetics through the redox and methylation influence of EAAT3-mediated cysteine uptake

• Online Access: http://hdl.handle.net/2047/d20002977

The level of oxidative stress increases with age, and abnormal elevations are a hallmark of many neurological and neuropsychiatric disorders, including Alzheimer's disease. In neurons, the glutamate, aspartate, and cysteine transporter EAAT3 is the predominant transporter of cysteine, the rate-limiting precursor for synthesis of glutathione, the primary intracellular antioxidant. Thus, the regulation of EAAT3 is crucial in maintaining redox balance in neurons, and agents that change its activity can exert important effects on neuronal redox status. Furthermore, since methylation is highly sensitive to redox status, these agents can also modulate methylation status, including DNA methylation, yielding epigenetic consequences.