Polyphenols neuroprotective effect in a Parkinson’s disease yeast model
Polyphenols neuroprotective effect in a Parkinson’s disease yeast model: phosphoproteome alterations
Background
Plant polyphenols been reported to have substantial neuroprotective activity. These compounds, formerly considered only as antioxidants, are now known to be able to activate various cellular mechanisms of action. Besides free radical scavengers, they are iron chelators, activators of survival genes and genes of signaling pathways and also could be regulators of mitochondria function.
Neurodegenerative diseases are multifactorial and currently there is no effective therapy against the progressive neuronal death characteristic of these pathologies. It is therefore very important to find new therapeutic strategies that can prevent and / or delay the neurodegeneration process. Studies in Disease and Stress Biology Lab revealed that polyphenols enriched fractions obtained from leaves and fruits of Portuguese endemic plants have high neuroprotective potential, increasing viability under conditions of oxidative stress and αSyn-induced toxicity due to aggregation, two features of Parkinson's disease. The objective of this proposal is to study the effect of these plants polyphenols subject or not to a digestive process in a yeast model of Parkinson's disease.
Working plan
The proposed work is in the frame of FCT project intitled “Polifenóis como agentes protectores em modelos celulares de alfa-sinucleinopatias, em particular na doença de Parkinson”, (PTDC/BIA-BCM/111617/2009) and will involve the following tasks:
TASK 1 - Analysis of alterations on phosphoproteome promoted by enriched and digested polyphenols fractions in yeast cells expressing αSyn.
This analysis will be done using two-dimensional gels of proteins and will require optimization of the technique involved. Using bioinformatic programs and databases available, the phosphoproteome map will be characterized.
TASK 2 - Identification of key signaling pathways, affected by polyphenols fractions in yeast cells expressing αSyn.
The proteins showing higher variations in the levels of phosphorylation will be identified by MS (external collaboration).
TASK 3 - Validation of the obtained results by complimentary analysis of phosphoproteome.
Changes in the levels of phosphorylation of proteins identified in task 2 will be confirmed by western blot. In parallel, the phenotypic analysis of mutants in genes encoding these proteins will relate their function with the polyphenols protective effect in the αSyn-induced toxicity.
Supervisors
Cláudia Nunes dos Santos (csantos@itqb.unl.pt, 214469651)
Sandra Tenreiro (stenreiro@fm.ul.pt, 21 7999441).
Laboratory/Institution
