In Parkinson Disease (PD), the aggregation of misfolded proteins called alpha-synuclein (a-syn), represents one of the major cellular hallmarks of the disease. Insoluble property of these aggregates make difficult their degradation, which disrupts the neuronal homeostasis and leads to neurodegeneration.
Several studies showed correlation between alterations of degradation systems (autophagic or proteasomal), implicated in the protein quality control, and a-syn aggregation. It’s important to know how an alteration of degradation systems is involved in the pathogenesis of PD.
Our group recently created a new cellular model in which we control the aggregation of a-syn optogenetically and observe it in real time. This system is called the LIPA (Light-Inducible Protein Aggregation) system, allowing us to induce aggregates in vitro and observe the effects over time. Degradation sytems activity is here mesured by using several specific markers, proteasomal and autophagic, which help us to investigate the relation between a-syn aggregation and the degradations systems.
Using this cellular model, we were able to observe the effect of LIPA-induced aggregates on the proteasomal system in cells for the first time. Moreover, we are interested in the inhibition of proteasomal and autophagic systems and its effect on the aggregation.
Our observations reveal LIPA system's ability to successfuly mimic the potential effects of a-syn aggregation on degradation systems in PD pathogenesis. So, by looking at potential actors implicated in the degradation of alpha-synuclein, we aim to further elucidate ways that can reverse the aberrant accumulation of this protein in PD.