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

Paired helical filament (PHF) tau is the principal component of neurofibriliary 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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature medicine 1995-07, Vol.1 (7), p.693-699
Hauptverfasser: Yan, Shi Du, Yan, Shi Fang, Chen, Xi, Fu, Jin, Chen, Ming, Kuppusamy, Periannan, Smith, Mark A., Perry, George, Godman, Gabriel C., Nawroth, Peter, Zweier, Jay L., Stern, David
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Paired helical filament (PHF) tau is the principal component of neurofibriliary 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.
ISSN:1078-8956
1546-170X
DOI:10.1038/nm0795-693