Diferential effects of alpha synuclein on intracellular trafficking

OVEJERO M; BISBAL M; CÁCERES A; ANASTASIA A

Congreso; XXXVI Congreso anual (virtual) de la Sociedad Argentina de Investigación en Neurociencias.; 2021

Sociedad Argentina de Investigación en Neurociencias.

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