Biophysical characterization of tau fibrils obtained under oxidative stress condition and its deleterious effects on SH-SY5Y cells

SEQUEIRA, SABRINA; GONZÁLEZ-LIZÁRRAGA, FLORENCIA; CHEHÍN, ROSANA NIEVES; SOCÍAS, SERGIO BENJAMÍN; ÁVILA, CÉSAR LUIS

Córdoba

Congreso; LI Reunión anual de la Sociedad Argentina de Biofísica; 2023

Sociedad Argentina de Biofísica

Alzheimer’s disease is a chronic progressive neurodegenerative condition characterized bythe accumulation of abnormally folded proteins (tau protein and β-amyloid peptide) andtheir subsequent amyloid aggregation. Although the precise mechanisms that trigger thispathology have not been fully elucidated, it is clear that aging and oxidative stressconstitute an important risk factors. Previous studies from our laboratory have shown thatin non-reducing environments tau protein aggregates in an amyloid-like manner. In thiswork we advance on the biophysical characterization of these species and study theirdeleterious effects on SH-SY5Y cell model. Under mild oxidative stress conditions tauprotein forms long unbranched fibrils with a concomitant exposure of hydrophobicpatches. Furthermore, these fibrils exhibit a tendency to disassemble when treated withdifferent denaturing agents. Upon addition of these fibrils to cell cultures, they are readilyinternalized in SH-SY5Y cells and seem to escape the endosomal-lysosomal pathway. Inthe cytosol tau aggregates impair mitochondrial activity and increase oxidative stressultimately leading to cell death. Collectively, our system provides a novel, simple butphysiologically relevant tool to model the effect of oxidative stress on the development ofAlzheimer disease.