Biophysical characterization of tau amyloid aggregation: possible neuroprotective mechanism of doxycycline in tauopathies

MEDINA, L.; SEQUEIRA, S.; VERA, CECILIA; GONZALEZ LIZARRAGA, F; RAMOS SOUZA BARBOSA, L; SOCIAS, B; RAISMAN-VOZARI, R; CHEHÍN, RN

Congreso; 2nd Federation of Latinoamerican and Caribbean Neuroscience Societies; 2016

Alzheimer´s disease (AD) is a neurodegenerative pathology histologically characterized by the extracellular accumulation of senile plaques consisting of Aβ peptide and intracellular amyloid aggregates, the neurofibrillary tangles (NFT). The later are made of amyloid aggregates of abnormally phosphorylated tau protein and the toxicity of its prefibrillar aggregates were demonstrated. This fact highlights tau amyloid aggregation as an essential event in AD neuronal death. Considering previous results in which oxidative stress induced the entrance of glicosaminoglicans to neuron, we first studied the influence of heparin on tau aggregation. Our results clearly showed that this polianionic molecule induced tau aggregation.Since tetracyclines have neuroprotective effect in animal models we studied doxycycline, a second generation tretracycline, on tau amyloid aggregation to unravel the molecular neuroprotective mechanism. By using different biophysical techniques like SAXS, IR, fluorescence spectroscopy and fluorescence microscopy we have demonstrated that heparin can induce tau aggregation with a sigmoidal behaviour. The presence of doxycycline inhibits the amyloid fibrils formation but oligomeric species are still formed. Doxicycline does not inhibit the GSK3-β activity, suggesting that the antibiotic did not bind to monomeric species.SAXS confirms the presence of tau oligomers induced by doxycyclineDoxycycline inhibits tau amyloid