Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer's Disease.
Tau hyperphosphorylation is a central event in the development of Alzheimer's Disease (AD). Protein phosphatase 2A (PP2A) heterotrimer formation is necessary for efficient dephosphorylation of the tau protein. S-Adenosylmethionine-dependent carboxyl methylation is essential for the assembly of PP2A heterotrimers. Epidemiological evidence indicates that elevated plasma homocysteine is an independent risk factor for AD. Homocysteine is a key intermediate in the methyl cycle and elevated plasma homocysteine results in a global decrease in cellular methylation. We propose that the PP2A methylation system is the link relating elevated plasma homocysteine to AD.
Vafai
Scott B
SB
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. sbvafai@princeton.edu
Stock
Jeffry B
JB
D000544:Alzheimer Disease / Q000097:blood / Q000201:enzymology / Q000209:etiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism
D016875:tau Proteins; D006710:Homocysteine; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2