Session: 7

PS7-04 | Differential effects of alpha synuclein on intracellular trafficking

Milagros Ovejero

Instituto Ferreyra (INIMEC-CONICET-UNC)

Alpha synuclein (AS) is a highly studied protein that is related to many neurodegenerative diseases such as Parkinson’s disease and a group of pathologies known as synucleinopathies. AS normal function is debated but it is known that (1) participates in the regulation of the presynaptic vesicle reserve, (2) it could have a chaperone activity and plays a role in the assembly of the SNARE complex, (3) it can interact with Rab GTPases and (4) is involved in vesicle recycling. Despite being a focus of study, the mechanism by which AS generates pathogenic effects is unclear. One of the most interesting hypothesis is the one that postulates that AS could be affecting intracellular trafficking (Lindquist Lab 2006; experiments in yeast). This trafficking defects can result in decreased synaptic and surface protein exposure, lower trophic factor support, and less membrane trafficking. Altogether, these consequences could result in neurodegeneration. In our work we focus on the study of intracellular trafficking under the effects of AS in primary neuronal cultures. For this study we use a state-of-the-art system to synchronize the intracellular trafficking to analyze ER-Golgi-dendrites vesicle dynamics. Surprisingly, we found that AS induces a delay in the intracellular trafficking of a mainly axonal protein (p75NTR), while a dendritic protein (transferrin receptor) was not affected. These results sheds light on the mechanism by which AS may be acting in neurodegenerative diseases.