INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
Protective effect of heparin-induced GAPDH oligomers on human SH-SY5Y neuroblastoma cells
Autor/es:
TORRES-BUGEAU, CLARISA M; AVILA CL; RAISMAN-VOZARI, RITA; PAPY-GARCIA, DULCE; ITRI, ROSANGELA; BARBOSA, LEANDRO R S; CHEHIN, ROSANA N
Lugar:
San Javier
Reunión:
Congreso; XLI Reunion Anual de la Sociedad Argentina de Biofisica; 2012
Institución organizadora:
Sociedad Argentina de Biofisica
Resumen:
Lewy bodies and Lewy neuritis, the neuropathological hallmarks of Parkinson´s disease, are mainly made of filamentous assemblies of alfa-synuclein (AS). Although the precise causes of cell death remain elusive, the misfolding and aggregation of AS has been suggested to be implicated in the pathogenesis of Parkinson´s disease. However, other macromolecules including tau, ubiquitin, GAPDH and glycosaminoglycans are routinely found associated with these amyloid deposits. GAPDH is a glycolytic enzyme which was well known for their central role in energy production. However, recent results suggest that GADPH possess highly diverse non-glycolitic function. Our previous results showed that GAPDH achieve the fibrillar aggregation state after its interaction with acidic membranes and heparin or heparan sulphate at physiological pH and temperature conditions. However, the role of GAPDH in the pathogenesis of Parkinson´s disease has been poorly studied. In the present work, the relationship between GAPDH and AS was shown as the oligomers of GAPDH are able to accelerate the kinetics of AS aggregation promoting their conversion into fibers which justifies the presence of the enzyme in Lewy bodies. Using undifferentiated dopaminergic neuron cultures demonstrated that GAPDH oligomers are able to decrease the toxic effects of AS oligomers. This protective effect seems to be mediated by the reduction of the activity on the membrane of AS oligomers. The results obtained in this study allow us to propose the association GAPDH-glycosaminoglycan as a novel therapeutic strategy to diminish the progression of Parkinson´s disease by eliminating the toxic species of AS.