Different supramolecular arrangement of GAPDH prefibrilar species could be relevant in the extracellular matrix proteosthasis

BALEANI M; SOCIAS SB.; BARBOSA L.; ITRI R.; AVILA C.; RAISMAN VOZARI R.; CHEHIN R

Congreso; 2nd FALAN Congress; 2016

Federation of Latin American and Caribbean Neuroscience Societies

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme that has been associated to neurodegenerative diseases since it colocalizes with alpha-synuclein in amyloid aggregates in post-mortem tissue of patients with sporadic Parkinson disease. In a previous work, we showed that glycosaminoglycans-induced GAPDH prefibrillar specie accelerates the conversion of alpha-synuclein to fibrils. Our results strongly suggest that the interplay between glycosaminoglycans, GAPDH and alpha-synuclein has a role in pathological states. Here we demonstrate that the toxic effect exerted by alpha-synuclein oligomers in dopaminergic cell culture was abolished in the presence of GAPDH prefibrillar specie. Considering that GAPDH could also be secreted outside the cell where glycosaminoglycans are present, it seems plausible that GAPDH protofibrils could be assembled in the extracellular space kidnapping the alpha-synuclein toxic oligomers. In the present work we demonstrate that the interaction of this multifunctional enzyme with acidic membranes or oxidatives species generate another supramolecular structutres that could interfere with this novel proteosthatic effect. In this context the structural and functional characterization of GAPDH supramolecular arrangements could give new insight to understand the complex mechanism that regulates the spreading of toxic species at extracellular level