Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β-peptide

Du Yan Shi Du Yan, Fang Yan Shi Fang Yan, X. Chen, J. Fu, M. Chen, P. Kuppusamy, M. A. Smith, G. Perry, G. C. Godman, P. Nawroth, J. L. Zweier, D. Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Paired helical filament (PHF) tau is the principal component of neurofibrillary tangles, a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD), Post-translational modification of tau, especially phosphorylation, has been considered a major factor in aggregation and diminished microtubule interactions of PHF-tau. Recently, it has been recognized that PHF-tau is also subject to non-enzymatic glycation, with formation of advanced glycation end products (AGEs). We now show that as a consequence of glycation, PHF-tau from AD and AGE-tau generate oxygen free radicals, thereby activating transcription via nuclear factor-κB, increasing amyloid β-protein precursor and release of ~4 kD amyloid β-peptides. These data provide insight into how PHF-tau disturbs neuronal function, and add to a growing body of evidence that oxidant stress contributes to the pathogenesis of AD.

Original languageEnglish (US)
Pages (from-to)693-699
Number of pages7
JournalNature Medicine
Volume1
Issue number7
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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