CHEMICALLY MODIFIED TETRACYCLINE INHIBITS ALPHA-SYNUCLEIN AMYLOID FIBERS FORMATION AND NEUROINFLAMMATION

GONZALEZ-LIZARRAGA, MF; SOCÍAS SB; AVILA CL; PLOPER, DIEGO; BARBOSA LR; MEDINA, L; FRANCIS N; ITRI R; PIETRASANTA, L; RAISMAN- VOZARI, R; CHEHÍN R

C.A.B.A.

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedades de Biociencias

Parkinson´s disease related death of dopaminergic neurons has been linked to pathological aggregation of α-synuclein (AS) protein and its transcellular traffic through the dopaminergic system. Tetracyclines, such as minocycline and doxycycline, have been shown tobe neuroprotective in Parkinson´s disease animal models. Neuroprotective activities of minocycline have been attributed to its inhibitory effects on microglia activation and doxycycline has been shown to protect cells by inhibiting the formation of toxic alpha synuclein species. Chemically modified tetracycline (CMT) has been proven to protect neurons through residual anti-inflammatory activity but their effects on AS are unknown. In the present work, we explore the ability of an specific CMT to inhibit the formation of amyloid aggregates of AS using different biophysical techniques such as fluorescence techniques, SAXS and advanced microscopies. In addition, we evaluate the ability of CMT to modulate the inflammatory response of microglial cultures mediated by different inflammogenic compounds.This study represents a milestone in the assessment of CMT as a therapeutic agent for the treatment of neurodegenerative disease.