Annonacin-induced α-synuclein fibrils increase ROS production in dopaminergic cell model: possible role in Guadalupe Island´s atypical Parkinsonism

GONZALES LIZARRAGA, MF; AVILA C.; SOCIAS, S.B.; SEPULVEDA DIAZ, J.; BARBOSA L.; BLESSING LD; NESKE A.; ITRI R.; RAISMAN VOZARI R.; CHEHÍN R.

San Miguel de Tucumán

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS); 2016

SAB - Sociedad Argentina de Biofísica

Annonacin is a chemical metabolite present in some fruits of the Annonaceae family, a traditional food in Guadeloupe Island, and has been indicated as the cause of atypical parkinsonian disorder which affect a notable percentage of the island population. Recent reports have shown that regular consumption in mice caused brain injuries consistent with Parkinson disease in a mechanism involving the inhibition of Complex I of the respiratory chain in mitochondria. Although the pathological aggregation of α-synuclein was signed as the essential molecular event in Parkinson disease, there are not reports on the effect of annonacin on α-synuclein aggregation. In this way, the aim of the present work is to gain knowledge on the effects of annonacin on the kinetics α-synuclein aggregation, as well as the toxicity of fibrillar species on dopaminergic cell model. By using transmission electron microscopy we have found that annonacin induces morphological changes in the fibrillar structure of α-synuclein. Through ThT fluorescence assay and small angle x-ray scattering we confirmed that annonacin is able to affect the kinetics of α-synuclein amyloid pathway. The fibers formed in the presence of annonacin display increased toxicity on dopaminergic cell model and trigger increased reactive oxygen species (ROS) production. Taken together, our results suggest that annonacin induced the production of α-synuclein fibers with increased toxicity on dopaminergic cell model.