title: Folic acid inhibits tau phosphorylation through regulation of PP2A methylation in SH-SY5Y cells.
abstract: OBJECTIVE
  Neurofibrillary tangles (NFTs), which are composed of intracellular filamentous aggregates of hyperphosphorylated tau protein, are one of the pathological hallmarks of Alzheimer's disease (AD). Because tau phosphorylation is regulated by phosphatases, abnormal metabolism of protein phosphatase 2A (PP2A) has been proposed to be a contributing factor to the disease process.
  
  
  RESULTS
  To determine the function of folic acid on tau phosphorylation, an in vitro model of human neuroblastoma cells (SH-SY5Y) were exposed to folic acid (0-40 μmol/L) for 96 h, in the presence or absence of the phosphoesterase inhibitor okadaic acid (OA) (10 nmol/L) for 9 h. The data of western blot showed tau phosphorylation at the Ser396 site in OA-incubated SH-SY5Y cells was inhibited by folic acid in a concentration-dependent manner, with the folic acid concentration of 40 μmol/L providing maximal inhibition. Folic acid can downregulate tau protein phosphorylation by inhibiting the demethylation reactions of PP2A. High folic acid concentrations (20 and 40 μmol/L) increased SAM:SAH ratios and cell viability.
  
  
  CONCLUSIONS
  Therefore, we can speculate that folate deficiency may be a cause of PP2A deregulation, which can in turn lead to expression of the abnormal hyperphosphorylated form of tau.
authors: Guowei Huang, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, P. R. China. Tel: +86-22-83336606. Fax: +86-22-83336603. E-mail: huangguowei@tmu.edu.cn.
authors: W
authors: W
authors: Li
authors: M
authors: M
authors: Jiang
authors: Y
authors: Y
authors: Xiao
authors: X
authors: X
authors: Zhang
authors: S
authors: S
authors: Cui
authors: G
authors: G
authors: Huang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005492:Folic Acid / Q000378:metabolism / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008745:Methylation / Q000187:drug effects; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000737:chemistry* / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D019319:Okadaic Acid; D005492:Folic Acid; D054648:Protein Phosphatase 2
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