The ‘golden age’ of DNA methylation in neurodegenerative diseases

Abstract

DNA methylation reactions are regulated, in the first instance, by enzymes and the intermediates that constitute the ' so called ' one-carbon metabolism. This is a complex biochemical pathway, also known as the homocysteine cycle, regulated by the presence of B vitamins (folate, B6, B12) and choline, among other metabolites. One of the intermediates of this metabolism is S-adenosylmethionine, which represent the methyl donor in all the DNA methyltransferase reactions in eukaryotes. The one-carbon metabolism therefore produces the substrate necessary for the transferring of a methyl group on the cytosine residues of DNA; S-adenosylmethionine also regulates the activity of the enzymes that catalyze this reaction, namely the DNA methyltransferases (DNMTs). Alterations of this metabolic cycle can therefore be responsible for aberrant DNA methylation processes possibly leading to several human diseases. As a matter of fact, increasing evidences indicate that a number of human diseases with multifactorial origin may have an epigenetic basis. This is also due to the great technical advances in the field of epigenetic research. Among the human diseases associated with epigenetic factors, aging-related and neurodegenerative diseases are probably the object of most intense research. This review will present the main evidences linking seve ral human diseases to DNA methylation, with particular focus on neurodegenerative diseases, together with a short description of the state-of-the-art of methylation assays.

Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome

“…Aberrant methylation patterns have been associated with various diseases including cancer and neurodegenerative diseases. 3,4 In addition, polymorphisms in genes involved in the folate metabolisms have been associated with cancer risk, including colorectal and gastric cancer, vascular disease, depression, and Down's syndrome. 5 Currently, there are evidences of an association between DNA methylation level and polymorphisms in folate metabolism genes.…”

B-Vitamins and One-Carbon Metabolism

“…Epidemiological studies have also investigated the role of the relevant B-vitamins, with the focus mainly on folate and vitamin B12. Studies involving populations with lower baseline folate status in general support the role of folate in cognitive dysfunction [160][161][162] and cognitive decline [163,164], whereas those in countries with food fortification policies and thus overall higher mean concentrations of folate, are generally less supportive for a role in cognitive dysfunction [165,166], cognitive decline [167][168][169] or dementia [170]. Similarly, a number of large cohort studies have associated low vitamin B12 status (using more sensitive biomarkers of status including MMA and HoloTC) with cognitive dysfunction [160,166,171] and cognitive decline [162,172,173] in older people.…”

“…Frequently, the vegetarian diet provides a high intake of n6PUFA and reduced contributions from n3PUFA, especially LC n3PUFA [168]. In addition to the possible link with HCY, excess n6PUFA can directly increase cardiovascular risk through the generation of proinflammatory eicosanoids and platelet aggregation [169]. For the above reasons, vegetarians should not underestimate Cbl intake through the appropriate use of supplements, while maintaining a balanced diet according to individual needs.…”

Special issue on advances and controversies in B vitamins and choline

“…Deficiency in B vitamins and choline are closely related to epigenetic modifications causing changes in gene expression, which have an impact on disease risk. This is thought to be especially important for two stages of life, the prenatal period and higher age.The relationship between age-associated diseases (such as dementia, osteoporosis and vascular diseases) and B vitamins has been a central research area during the past decades [ 1 ]. Of particular importance is the potential role of vitamins in disease prevention.…”

“…The relationship between age-associated diseases (such as dementia, osteoporosis and vascular diseases) and B vitamins has been a central research area during the past decades [ 1 ]. Of particular importance is the potential role of vitamins in disease prevention.…”