Analysis of ER and mitochondria dynamics and interaction during protein aggregation
| Grant number: | 12/15495-2 |
| Support type: | Regular Research Grants |
| Duration: | May 01, 2013 - April 30, 2015 |
| Field of knowledge: | Biological Sciences - Morphology |
| Principal Investigator: | Merari de Fátima Ramires Ferrari |
| Grantee: | Merari de Fátima Ramires Ferrari |
| Home Institution: | Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
Loss of dopaminergic neurons and protein aggregates containing alpha-synuclein are the meain cellular features of Parkinson's disease. However, cellular impairment is presente even before these aggregates, which may be of relevance to cell death. Stem cells are good models to study neurodegenerative diseases. Induced-pluripotent stem cells also allow the investigation of cellular functions in individuals affected by neurodegenerative diseases. In view of this, the objectives of the presente study are: implement the technique of derivation of dopaminergic neurons from embryonic stem cells and from fibroblasts; study the influence of calcium during the early phase of neurodegeneration, as well as evaluate mitochondria trafficking and the autophagy system in these neurons in the presence and absence of alfa-synculein aggregates. To this end, human embryonic stem cell and fibroblasts induced to pluripotency, by the expression of SOX2, c-MYC, OCT4 and KFL4, of patients diagnosed with idiopathic Parkinson's disease will be cultivated. Stem cells will be differentiated into dopaminergic neurons and submitted to fura-2 calcium labeling, expression of alpha-synuclein and mutant miro, as well as activation and repression of autophagy in order to comprehend some of the major cellular events occuring during the initial phase of dopaminegic neurodegeneration. (AU)