Galante Denise, Tomaselli Simona, Florio Tullio, Mario Nizzari, Gatta Elena, Corsaro Alessandro, Perico Angelo, D'Arrigo Cristina
Galante Denise, Perico Angelo, D'Arrigo Cristina: Institute for Macromolecular Studies, National Research Council, 16149 Genova, Italy Gatta Elena: Department of Physics, University of Genoa, 16100 Genova, Italy Florio Tullio, Mario Nizzari, Corsaro Alessandro:3Section of Pharmacology, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genova, 16132 Genova, Italy Tomaselli Simona:Institute for Macromolecular Studies, National Research Council, 20133 Milano, Italy
Extracellular plaques of amyloid-? (A?) are the main histopathological signatures of Alzheimer's disease (AD). In vitro and in vivo analysis of amyloid deposits in AD revealed various N- and C-terminal variants, in addition biochemical studies showed that A? peptides isolated from AD brains were post-translationally modified. N-terminal deletions and pyroglutamylation enhance aggregation of A? into neurotoxic species and such peptides may initiate or nucleate the pathological deposition of A? into plaques. Among these, A?pE3-42 strongly affects cultured neuron and astrocyte survival. In the last years, a new molecular actor has appeared in AD pathophysiology: the cellular prion protein (PrPC). The role of this protein is still not completely disclosed, but its involvement in the complex pathway connecting A? to Fyn/Tau neuronal toxicity is now recognized. In particular, the trigger of the molecular cascade leading to synapses impairment and cellular death seems to be the direct interaction of A? oligomers (A?o) with PrPC. In this work we exploit the interactions between A? peptides and N-terminal truncated PrPC. In particular we study the effect of PrPc (90-231) on aggregation of A?1-42, A?pE3-42 and of their mixtures. To reach this goal we investigated the different interactions by NMR and we characterized the intermediate species by turbidimetry, circular dichroism, transmission electron microscopy, ThT and ANS fluorescence. To determine if PrPC is a mediator of A?-induced neurotoxicity, we studied the physiological response of cells to A?o, and the dysregulation of calcium homeostasis, both on glioblastoma cells where PrPC expression was inhibited or not
XXIII National Congress of Pure and Applied Biophysics Society, Cortona (AR), 18-21/09/2016,
amyloid beta, prion protein, interaction
Perico Angelo, Galante Denise, Tomaselli Simona, D Arrigo Cristina
ID: 365480
Year: 2016
Type: Presentazione
Creation: 2017-01-24 15:29:28.000
Last update: 2017-01-25 14:58:51.000
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CNR OAI-PMH: oai:it.cnr:prodotti:365480