Natacha Coppieters and Mike Dragunow Pages 3398 - 3412 ( 15 )
Epigenetic alterations have been associated with several human diseases including Alzheimers disease (AD). AD is a complex neurodegenerative disease characterized by a progressive decline in cognitive functions, neuronal cell loss and by the presence of β amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the cortex. Mutations in specific genes have been identified but can only explain a small percentage of the AD cases. The origins of the sporadic cases of AD are still not known but there is evidence for a role of epigenetics in the etiology of the disease. In this review we focus on discussing the roles of DNA methylation and hydroxymethylation in the development and potential treatment of AD. We discuss papers showing that there are alterations in methylated cytosine (5mC) levels in AD and also highlight the potential role of hydroxylated methylcytosine (5hmC) in the epigenetic regulation of brain gene expression and perhaps in AD. We discuss the potential influence of environmental factors, working through epigenetic mechanisms, on increasing the risk of developing AD and their potential in treating this major neurodegenerative disorder.
Alzheimer's disease, DNA methylation, epigenetics, 5-methylcytosine, 5-hydroxymethylcytosine, environment, pronucleus, aging, neurons, oxidative stress
Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, New Zealand.