Effect on SH-SY5Y cells of amyloid-like tau fibrils obtained under mild oxidative conditions

SEQUEIRA, SABRINA; GONZÁLEZ LIZARRAGA, MARÍA FLORENCIA; CHEHÍN, ROSANA NIEVES; SOCIAS, SERGIO BENJAMÍN; ÁVILA, CÉSAR LUIS

Rosario

Congreso; L Reunión anual de la Sociedad Argentina de Biofísica; 2022

Sociedad Argentina de Biofísica

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder associated with the accumulation of neurofibrillary tangles (NFTs) in the human brain. The major constituent of NFT is the microtubule-associated protein tau that is abnormal phosphorylated and deposited into an amyloid like aggregate. The causes of tau aggregation have not yet been clarified, but there is evidence suggesting that oxidative stress-related modifications could play a significant role. In this way, the major objective of this study was to investigate the effect of mild oxidative conditions on tau aggregation. By employing a Thioflavin T fluorescence assay we observed the formation of amyloid-like aggregates upon removal of reducing agents from recombinant full-length tau (hTau40). The fibrillar structure of the aggregates was further confirmed by transmission electron microscopy. Most interestingly, these species were able to trigger cytotoxic effects on SH-SY5Y cells as monitored by both MTT and LDH assays. Moreover, we observed that these tau aggregates were incorporated into the cells and accumulated within the cytoplasm. Further work is needed to unravel the mechanisms leading to cytotoxicity and to inquire if the species obtained here are capable of recruiting endogenous tau and trigger its aggregation.