Hyperphosphorylation results in tau dysfunction in DNA folding and protection

Yang Lu, Hai Jin He, Jun Zhou, Jun Ye Miao, Jing Lu, Ying Ge He, Rong Pan, Yan Wei, Ying Liu, Rong Qiao He

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies.

Original languageEnglish
Pages (from-to)551-563
Number of pages13
JournalJournal of Alzheimer's Disease
Volume37
Issue number3
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Keywords

  • Alzheimer's disease
  • DNA protection
  • formaldehyde
  • GSK-3β
  • phosphorylation
  • tau hyperphosphorylation
  • tau protein
  • tauopathy

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