PAZEPC INDUCES CONFORMATIONAL CHANGES IN TAU PROTEIN LEADING TO AGGREGATION

SEQUEIRA, SABRINA; ÁVILA, CÉSAR LUIS; CHEHÍN, ROSANA NIEVES

Santos

Congreso; XLII Congress of the Brazilian Biophysical Society; 2017

Sociedad Brasilera de Biofísica

Alzheimer?s disease (AD) is an age-related neurodegenerative disorder associated with abnormal phosphorylation and amyloid aggregation of Tau protein that culminates with the formation of neurofibrillary tangles (NFTs) in the human brain. The causes of these changes in Tau protein have not yet been clarified, but there is evidence suggesting that oxidative stress may be implicated in the etiopathogenesis of AD. Increased levels of oxidative stress markers, including the markers of lipid peroxidation products, are found in brains of AD subjects. It has been shown that lipids exert a profound influence on the secondary structure of Aβ, another peptide implicated in AD, in some cases including the formation of amyloid fibrils. Particularly, there is evidence indicating that Tau protein is able to polymerize in vitro in the presence of lipid peroxidation products, but the molecular mechanism of this process is unclear. We therefore studied the influence of oxidized lipids, such as POPC or its oxidation derivative PazePC on the conformation of Tau. We observed an increase in the turbidity of a solution containing Tau protein and large unilamellar vesicles of POPC:PazePC (1:1) after 24 hours of incubation. The change in turbidity arises from an increase in the scattering of the solution as monitored with small angle X ray scattering. Conformational changes in Tau protein upon contact with lipid vesicles were also monitored by Fourier Transform Infrared Spectroscopy. The results presented herein allow a better understanding on the mechanisms leading to changes in the conformation of tau. Further work is needed to inquire into the impact of these conformational changes on the phosphorylation pattern of aggregated tau