INVESTIGADORES
SOCIAS Sergio Benjamin
congresos y reuniones científicas
Título:
Chemically modified tetracycline incyniclide inhibits neuroinflammation and alpha-synuclein pathological aggregation
Autor/es:
GONZALES LIZARRAGA, MF; SOCIAS, S.B.; AVILA C.; PLOPER D.; FRANCIS N.; MEDINA L.; ROCCA J.; RAISMAN VOZARI R.; CHEHÍN R.
Lugar:
Buenos Aires
Reunión:
Workshop; Symposium:The role of glial cells in health and disease of the Nervous System: Clinical and Basic Science walking together.; 2017
Resumen:
Tetracyclines antibiotics family have demonstrated interesting activities in neuroprotective studies. These effects have been attributed to their inhibitory effects on alpha synuclein pathologic aggregation as well as on microglia activation. However, the antibiotic activity of these compounds limit their prescription for chronic treatments such as neurodegenerative disorders. Thus, chemically modified tetracyclines with diminished or reduced antibiotic activity could represent a more adequate therapy for long-term treatments. In this regard, it was recently reported that the chemically modified tetracycline incyclinide (also known as COL-3) lacks antibiotic activity but retains anti-inflammatory effects. In the present study we evaluate the ability of incyclinide to inhibit alpha-synuclein aggregation, as well as its capacity to modulate the inflammatory response of microglial cultures. By using different inflammogenic compounds, we demonstrate that incyclinide inhibits cytokine production and Iba-1 release, as well as expression of prototypical markers of microglial activation. Considering that incyclinide has reduced antibiotic activity compared to other tetracyclines and is a well tolerated drug according to cancer-related Phase I clinical trials, we conclude that it could be a ?ready to use drug?. Due to its ability to diminish toxic aggregation of alpha synuclein as well as neuroinflammatory processes, we propose incyclinide is poised as an promising candidate for Phase I clinical trials in neuroprotection.