GAPDH: MANY PATHWAYS TO AMYLOID LIKE AGGREGATION DEPENDING ON THE ENVIRONMENT

BALEANI, MÓNICA ANDREA; ROSANGELA ITRI; CHEHÍN, ROSANA NIEVES; LEANDRO S. BARBOSA; PAPY-GARCÍA DULCE; GONZÁLEZ LIZARRAGA, MF; AMZEL, M; AVILA, CÉSAR LUIS

Santos, Sao Paulo

Congreso; XLII Congress of the Brazilian Biophysical Society (SBBf); 2017

Sociedad Brasilera de biofísica

Glyceraldehide-3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme that is known as a ?moonlight? protein, due to its diverse functions in addition to its role in energy production. It has been associated to neurodegenerative diseases, but its precise role in these pathologies remains unclear. Previously, we have demonstrated that GAPDH is able to assemble into protofibrils upon interaction with glycosaminoglycans, such as heparin or heparan sulphate.These GAPDH protofibrils are capable of sequestering alpha-synuclein toxic oligomers, which are involved in Parkinson Disease (PD). Considering that GAPDH can also be secreted from the cell towards the extracellular matrix where glycosaminoglycans are present, it seems plausible that these protofibrils could be assembled in the extracellular space kidnapping the alpha-synuclein toxic oligomers, a feature that could be exploited for neuroprotection in PD.However, we have also observed that the interaction of GAPDH with acidic membranes or oxidant species generates another supramolecular structure that could interfere with its neuroprotective effect. In damaged or aging brains, glycosaminglycans, acidic membranes and oxidant species coexist. In this context, the structural and functional characterization of GAPDH supramolecular arrangements could give new insight for understanding the complex mechanisms of neurodegeneration.