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

MEDINA L.; SEQUEIRA S.; VERA C.; GONZALES LIZARRAGA, MF; BARBOSA L.; SOCIAS, S.B.; RAISMAN VOZARI R.; CHEHÍN R.

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

Federation of Latin American and Caribbean Neuroscience Societies

Alzheimer's disease (AD) is a neurodegenerative Taupathology histologically characterized by theextracellular accumulation of senile plaques consistingof Aβ peptide and intracellular amyloid aggregates, theneurofibrillary tangles (NFT). The later are made ofamyloid aggregates of abnormally phosphorylated tauprotein and the toxicity of its prefibrillar aggregateswere demonstrated. This fact highlights tau amyloidaggregation as an essential event in AD neuronal death.Considering previous results in which oxidative stressinduced the entrance of glicosaminoglicans to neuron,we first studied the influence of heparin on tauaggregation. Our results clearly showed that thispolianionic molecule induced tau aggregation.Since tetracyclines have neuroprotective effect inanimal models we studied doxycycline, a secondgeneration tretracycline, on tau amyloid aggregation tounravel the molecular neuroprotective mechanism. Byusing different biophysical techniques like SAXS, IR,fluorescence spectroscopy and fluorescencemicroscopy we have demonstrated that heparin caninduce tau aggregation with a sigmoidal behaviour. Thepresence of doxycycline inhibits the amyloid fibrilsformation but oligomeric species are still formed.Doxicycline does not inhibit the GSK3-β activity,suggesting that the antibiotic did not bind tomonomeric species.