Loading...

165 | Alpha synuclein selectively affects intracellular trafficking dynamics

Disorders of the Nervous System

Author: Milagros Ovejero | email: movejero@immf.uncor.edu


Milagros Ovejero , Mariano Bisbal , Alfredo Cáceres , Agustín  Anastasía 1°2°

1° Instituto Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina
2° Instituto Universitario de Ciencias Biomedicas de Cordoba (IUCBC), Córdoba, Argentina

Intracellular trafficking is an extremely complex process that is highly regulated in neurons since this cell type has a particular architecture in which the correct functioning of the exocytic pathway plays a fundamental role for its survival. Alpha synuclein (AS) is a widely studied protein for its role in different neurodegenerative diseases such as Parkinson’s disease and a group of pathologies called synucleinopathies. Despite being the focus of several studies, its normal function it is still partly unknown and the manner in which this protein is involved in neuronal death is still not clearly known. One of the most interesting hypothesis suggests that AS may be affecting intracellular trafficking and thus affecting neuronal survival (Lindquist Lab 2006; experiments in yeast). Our focus is to study the effects of AS on the intracellular trafficking in mammalian neurons. We use a special system that allows us to synchronize the exocytic pathway and thus analyze if there are changes in the dynamics of protein trafficking. Using this synchronization system, we found that AS affects protein trafficking, but not in a general way. Instead, our results suggest that AS acts on the fission machinery of axonal trafficked proteins, but not somato-dendritic targeted proteins. These findings shed light on the mechanism by which AS may be acting in neurodegenerative diseases.