Chemically Modified Tetracyclines Inhibits α-synuclein Amyloid Fibers Formation and Neuroinflammation

GONZALES LIZARRAGA, MF; SOCIAS, S.B.; AVILA C.; PLOPER D.; BARBOSA L.; MEDINA L.; FRANCIS N.; ITRI R.; PIETRASANTA L.; RAISMAN VOZARI R.; CHEHÍN R.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Parkinson?s disease related death of dopaminergic neurons hasbeen linked to pathological aggregation of α-synuclein (AS) proteinand its transcellular traffic through the dopaminergic system. Tetracyclines,such as minocycline and doxycycline have been shown tobe neuroprotective in Parkinson?s disease animal models. Neuroprotectiveactivities of minocycline have been attributed to its inhibitoryeffects on microglia activation and doxycycline has been shownto protect cells by inhibiting the formation of toxic alpha synucleinspecies. Chemically modified tetracycline (CMT) has been proven toprotect neurons through residual anti-inflammatory activity but theireffects on AS are unknown. In the present work, we explore the abilityof an specific CMT to inhibit the formation of amyloid aggregatesof AS using different biophysical techniques such as fluorescencetechniques, SAXS and advanced microscopies. In addition, we evaluatethe ability of CMT to modulate the inflammatory response ofmicroglial cultures mediated by different inflammogenic compounds.This study represents a milestone in the assessment of CMT as atherapeutic agent for the treatment of neurodegenerative disease.