Intracellular trafficking defects induced by α-synuclein as a pathogenic mechanism for Parkinson?s disease.

MILAGROS OVEJERO; THOMAS M. JOVIN; AGUSTÍN ANASTASÍA GONZALEZ; VAISHALI SHARMA; DONNA J. ARNDT-JOVIN; MARIANO BISBAL; ALFREDO CACERES

Cordoba

Congreso; SAN 2018; 2018

Sociedad Argentina de Investigación en Neurociencias

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons of the substantia nigra. One of the hypotheses regarding the molecular mechanisms involved in the development of this disease postulates that defects in the intracellular protein and/or membrane trafficking is an initial event in the pathogenesis of this disorder. It is well known that increased expression of α-synuclein is associated with a higher incidence of PD. However, the underlying cellular and molecular mechanisms remains to be elucidated. We utilized a state-of-the-art system to synchronize the secretory pathway in order to study if α-synuclein is capable to affect the dynamics of vesicular transport between the endoplasmic reticulum (ER) and the Golgi apparatus, and the vesicle release from the latter. This system is based in fusion proteins that aggregates in the ER and can be synchronously released to the Golgi apparatus by a membrane permeable drug. Interestingly, we found that the expression of α-synuclein induces a delay in the proteins transport between the ER and the Golgi apparatus, and also a delay in the vesicle exit from the Golgi apparatus towards the neuronal processes. These results suggest that the toxicity of α-synuclein may be due, at least in part, to the delay or blockage of the exocytic pathway.