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 language | English (US) |
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Pages (from-to) | 693-699 |
Number of pages | 7 |
Journal | Nature Medicine |
Volume | 1 |
Issue number | 7 |
State | Published - 1995 |
Externally published | Yes |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Medicine