Cellular and Molecular Neurobiology
Author: Milagros Ovejero | Email: movejero@immf.uncor.edu
Milagros Ovejero 1°, Mariano Bisbal 1°, Alfredo Caceres 2°, Agustin Anastasia 1°
1° Instituto Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
2° Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.
Defects in intracellular trafficking have been described as a common mechanism in neurodegenerative diseases. One of the most studied proteins in relation to nervous system diseases is Alpha Synuclein (AS) protein. While it is known to be related to Parkinson’s disease and synucleinopathies, the mechanisms by which this protein induces neurodegeneration remain unknown. In this study, we investigated the effects of the AS protein on intracellular trafficking. For this purpose, we used primary cultures of rat hippocampal neurons and a synchronization system of the exocytic pathway. Here, we demonstrate that the AS protein induces selectively defects in intracellular trafficking. We used two models to study the exocytic pathway, the p75NTR receptor, and the Transferrin receptor (TfR). Our results indicate that only the trafficking of the p75NTR receptor was altered, while that of TfR remained unchanged. Apparently, the mechanism by which AS affects intracellular trafficking is through the modification of the actin cytoskeleton, altering the fission from the Golgi of p75NTR vesicles, whose fission machinery requires Dynamin anchoring to actin filaments. Surprisingly, we managed to rescue the observed effect on intracellular trafficking using CofilinS3A. It is worth noting that this mutant Cofilin also managed to reverse the effects of AS on neuronal cytoarchitecture. The findings described here help to understand the mechanisms by which AS may be inducing neurodegeneration.