INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
Design of a molecule capable of inducing the formation of neuroprotective protofibrils of GAPDH
Autor/es:
BALEANI, MONICA; AVILA, CESAR LUIS; PAPY-GARCIA, DULCE; CHEHIN, ROSANA
Lugar:
Salto
Reunión:
Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015
Resumen:
Parkinson disease (PD) is one of the most important neurodegenerativedisorders with motor alterations resulting from the loss of dopaminergicneurons in the substantia nigra. The loss of neurons is caused by toxicoligomeric species of alfa-synuclein (AS). We demonstrated that ASoligomers can be recruited by protofibrillar species of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) abolishing its toxic effect1formation of this neuroprotective GAPDH protofibril could be triggered invitro by heparin. Since heparin has a strong anticoagulant activity, our goalis to find a compound capable of promoting GAPDH agregation withoutafecting the coagulation cascade. In this way using Thioflavin T assay wefound several heparan-mimetics able to induce GAPDH aggregation. Usingthe liposomal leakage test we also evaluated the capability of GAPDHprotofibril to prevent the disruption of reconstituted membrane by the ASoligomers.These results represent an important first step towards the development ofneuroprotective compunds to be used in the treatment of PD.[1] Ávila CL, et al. J Biol Chem 289:13838-50, 2014. Acknowledgements:Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).Support: PIP 0183 ? CONICET.PICT 2012- 2882 ? AGENCIA.