New screening method to identify antiprions

Identifier:  TFG:2196

Handle: https://hdl.handle.net/20.500.11797/TFG2196

Authors:  Cerdán Porqueras, Víctor

Abstract:
Protein aggregates are the cause of several human pathologies such as Alzheimer’s disease, Huntington disease or Parkinson disease. The aggregation of proteins can be produced by several reasons and in some cases, it presents a prionic characteristics. These prionic characteristics produce the transmission of the protein misfolding and its aggregation, exacerbating the symptoms of the disease. Despite recent advances in understanding how these aggregation mechanisms work, our knowledge in avoiding them and treating these diseases is still very limited. In this work, S. cerevisiae has been used as a model to establish a methodology that allow us to perform a screening of peptides with antiprionic characteristics. This methodology is based in the hypothesis that variations of the prionic proteins might be able to interfere in the aggregation of their original form, thus stopping the disease progression. The results obtained show that the methodology of a double selection, by growth and fluorescence, is resolutive enough to identify mutated peptides that are able to avoid aggregation. Additionally, it has been observed an augmented cellular volume in those yeasts presenting aggregates, which suggests that they are able to detect these aggregates and stop they cell cycle to avoid transmitting them to their descendance. This cell cycle halt would be responsible of the augmented cellular volume. The results obtained will allow to continue the research to identify antiprionic peptides and to start a new research line to elucidate how yeast are capable of detecting and producing a response to the aggregates. A better understanding in these fields would allow us to characterize the biological mechanisms that prevent aggregation and develop treatments to treat it.