PYROGLUTAMYLATED AMYLOID-beta AFFECTS THE STRUCTURE, MORPHOLOGY AND TOXICITY OF THE FULL LENGTH BY SMALL QUANTITIES
| Autor: | Galante Denise, Ruggeri F.S., Pellistri Francesca, Elena Gatta, Tullio Florio, Angelo Perico, Simona Tomaselli, Cristina D'Arrigo |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The 12th international conference on Alzheimer's&Parkinson's diseases AD/PD2015, Nizza, 18-22/03/2015 info:cnr-pdr/source/autori:Galante Denise, Ruggeri F.S., Pellistri Francesca, Elena Gatta, Tullio Florio, Angelo Perico, Simona Tomaselli, Cristina D'Arrigo/congresso_nome:The 12th international conference on Alzheimer's&Parkinson's diseases AD%2FPD2015/congresso_luogo:Nizza/congresso_data:18-22%2F03%2F2015/anno:2015/pagina_da:/pagina_a:/intervallo_pagine |
| Popis: | Objectives: to determine which is the ratio in the mixture of A?py3-42 and A?1-42, where A?py3-42 has the major influence on the aggregation kinetics, secondary structure, morphology and toxicity of A?1-42. Methods: We characterized the cell toxicity by analysis of the deregulation of the calcium; aggregation kinetics by turbidity assay; conformational analysis by Circular Dichroism; morphological characterization by TEM and AFM; secondary structure determination by NanoIR. Results: The different mixtures and peptides alone were differently effective in inducing free Ca2+ increase in the exposed cells, but the 5% mixture showed the higher increase of fluorescence. The conformational analysis showed that the 5% mixture has an intermediate curve trend between A?1-42 and A?py3-42 alone. The turbidity assay showed faster aggregation kinetics for A?py3-42 and slower aggregation rates for A?1-42, the 5% mixture showed the aggregation kinetics more similar to those of A?py3-42. Morphological analysis revealed in A?py3-42 and 50% mixture big aggregates and few fibers, in the other mixtures and A?1-42 short protofibrils and small spheroidal aggregates and in the 5% mixture large spheroidal aggregates. The NanoIR showed about A?1-42 aggregates only in ?-helix and in ?-helix and ?-sheet, about A?py3-42 exclusively in ?-sheet and about 5% mixture in random coil and in a mixture of ?-helix and ?-sheet with more ?-sheet. Conclusions: here we showed that A?py3-42 revealed its maximum effective in the 5% mixture. This finding correlates with the presence of low concentrations of A?py3-42 in the core of aggregates extracted from cerebral deposits |
| Databáze: | OpenAIRE |
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