Folate deprivation increases tau phosphorylation by homocysteine-induced calcium influx and by inhibition of phosphatase activity: Alleviation by S-adenosyl methionine.
Several recent studies have indicated that increased levels of homocysteine (HC), including that resulting from deficiency in folate, increases tau phosphorylation. Some studies indicate that this is accomplished via HC-dependent activation of NMDA channels and resultant activation of calcium-dependent kinase pathways, while others suggest that the increase in tau phosphorylation is derived via HC-dependent inhibition of methylation of phosphatases and resultant inhibition of phosphatase activity. We demonstrate herein in SH-SY-5Y human neuroblastoma that both of these phenomena contribute to the increase in phospho-tau immunoreactivity following folate deprivation, and that supplementation with S-adenosyl methionine (SAM) prevents both the increase in kinase activity and the decrease in phosphatase activity. These findings demonstrate that the divergent neuropathological consequences of folate deprivation includes multiple pathways that converge upon tau phosphorylation, and further support the notion that dietary supplementation with SAM may reduce or delay neurodegeneration.
Chan
Amy Y
AY
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.
Alsaraby
Ayat
A
Shea
Thomas B
TB
D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000188:drug therapy* / Q000378:metabolism*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016875:tau Proteins; D006710:Homocysteine; D019319:Okadaic Acid; D016202:N-Methylaspartate; D012436:S-Adenosylmethionine; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium