INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
The involvement of CHICUP dityrosine cross-linking in tau pathologic assembly: implicance in Alzheimer?s disease.
Autor/es:
SEQUEIRA, S; CHEHIN, RN; AVILA, CL
Lugar:
La Plata
Reunión:
Congreso; XLVII Reunión Anual de la SAB; 2018
Institución organizadora:
Sociedad Argentina de Biofisica
Resumen:
Alzheimer?s disease (AD) is an age-related neurodegenerative disorder associated with amyloid aggregation of tau protein in neurofibrillary tangles (NFTs) in human brain. The causes of tau aggregation have not yet been clarified, but the oxidative stress and metal rich environments have been implicated in triggering the toxic assembly. Besides the extensive damage on protein, lipid and nucleic acids reported under oxidative stress, it has also been implicated in dityrosine cross- linking formation in Amyloid-β (Aβ) through a metal catalyzed oxidation (MCO) process. Moreover, recent studies revealed the presence of these dityrosine crosslinks in ex-vivo Lewy ́s body from brain tissue in Parkinson disease (PD) patients. Similar α-synuclein aggregates were obtained in vitro via MCO in the presence of Cu2+ and hydrogen peroxide. This reaction is specifically called CHICUP (Copper and Hydrogen Peroxide Induced Cross-Linking of Unmodified Proteins) and its physiological relevance was proposed due to its brain-occurring chemistry.Despite the old relationship between impaired Cu2+ homeostasis and AD, its role in the ethiopathology remains unraveled. Surprisingly, there are not extensive studies on the MCO effect on tau except for the binding of Cu2+ to a 198 aminoacid fragment of the protein inducing a limited amount of aggregation, measured by dynamic light scattering (DLS). In this context, the main purpose of this study was to go in depth in how Cu2+ could be involved in tau aggregation and whether oxidative stress promotes the environment for the MCO. For this purpose, we have studied the effect of Cu2+ in the presence of hydrogen peroxide on tau by monitoring the formation of dityrosine cross-links through biophysical techniques. The results obtained herein allows us to get a better understanding on how Cu2+ and hydrogen peroxide, trigger dityrosine cross-linked tau aggregates which may behave as seeds in tau NFT formation and AD development.