Unraveling the amyloid beta attraction for the prion protein
| Autor: | Galante Denise, Tomaselli Simona, Florio Tullio, Mario Nizzari, Gatta Elena, Corsaro Alessandro, Perico Angelo, D'Arrigo Cristina |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | XXIII National Congress of Pure and Applied Biophysics Society, Cortona (AR), 18-21/09/2016 info:cnr-pdr/source/autori:Galante Denise, Tomaselli Simona, Florio Tullio, Mario Nizzari, Gatta Elena, Corsaro Alessandro, Perico Angelo, D'Arrigo Cristina/congresso_nome:XXIII National Congress of Pure and Applied Biophysics Society/congresso_luogo:Cortona (AR)/congresso_data:18-21%2F09%2F2016,/anno:2016/pagina_da:/pagina_a:/intervallo_pagine |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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