Toll-like receptor 3 mediated hyperphosphorylation of tau in human SH-SY5Y neuroblastoma cells

Authors

  • BEGUM NURUN NESSA md ,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • TOSHIHISA TANAKA md , phd,

    Corresponding author
    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • KOUZIN KAMINO md , phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • GOLAM SADIK phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • ASHIK BIN ANSAR md ,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • RYO KIMURA phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • HISASHI TANII md , phd,

    1. Department of Psychiatry, Mie University, Mie, Japan
    Search for more papers by this author
  • MASAYASU OKOCHI md , phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • TAKASHI MORIHARA md , phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • SHINJI TAGAMI md , phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • TAKASHI KUDO md , phd,

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author
  • MASATOSHI TAKEDA md , phd

    1. Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, Osaka, Japan,
    Search for more papers by this author

Toshihisa Tanaka, MD, PhD, Course of Advanced Medicine, Department of Post Genomics and Disease, Division of Psychiatry and Behavioral proteomics, Osaka University Graduate school of Medicine, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan. Email: tanaka@psy.med.osaka-u.ac.jp

Abstract

Abstract  Neurofibrillary tangles of abnormally phosphorylated tau are one of the characteristic pathological hallmarks of Alzheimer's disease (AD). In addition, immunological and inflammatory changes including complements and activated microglia are also common phenomena in AD. However, these pathological changes are yet to be interlinked in a common explainable background. In this study, the relevant mechanism of phosphorylation of tau protein and an innate immune signal transduction system were investigated. Toll-like receptor 3 (TLR3) is a receptor working in the innate immune system and its expression in the brain has already been reported. Total RNA was isolated from SH-SY5Y cells and reverse transcriptase polymerase chain reaction was done to see endogenous expression of TLR3 in SH-SY5Y cells that was further confirmed at protein level by Western blot analysis. Cells were treated with 50 µg/mL of polyinosinic–polycytidylic acid (pIpC), a synthetic analog of dsRNA and the changes of phosphorylation of tau protein were investigated. Further the level of phosphorylation of tau protein was investigated after the cells had been previously treated with 10 ng/mL of lipopolysaccharide (LPS) for 6 h to induce over-expression of TLR3. Increased phosphorylation of tau protein at PHF-1 site (Ser396/404), activation of Jun N-terminal kinase and p38 MAPK were observed in cells treated with pIpC. These effects were enhanced when cells were pretreated with LPS, a known transducer of TLR3. These data suggest that toll-like receptor 3, an innate immune molecule, might be a potential link to mediate hyperphosphorylation of tau in neurodegenerative processes of AD.

Ancillary