Human embryonic stem cells derived neurons exhibit impaired mitochondrial transport under oxidative stress and alpha-synuclein overexpression

DIMOPOULUS N; POZO-DEVOTO V; GARCIA C; SCASSA E; SEVLEVER G; FALZONE T

San Pablo

Congreso; VII Brazilian Congress on Stem Cells and Cell Therapy (ISSCR); 2012

ISSCR

Human neurodegenerative disorders such as Parkinson’s Disease (PD) are characterized by early axonal pathologies with abnormal accumulations of organelles and proteins leading to neuronal death. Biochemical and pathological studies suggest that both duplication and point mutations of the alpha-synuclein gene found in familial PD can lead to mitochondrial respiratory failure and oxidative stress. We tested the hypothesis that mitochondrial transport defects can be found at the initial abnormal phenotype leading to impaired mitochondrial function. Given the proven difficulty to reproduce classical pathologies of neurodegenerative diseases and proper human protein interaction in animal models, we have undertaken the first steps towards the utilization of human embryonic stem cells (hESC) derived neurons to study mitochondrial transport under experimental conditions that resemble these disorders. Our results suggest that mitochondrial transport defects are triggered at the onset of the impairments observed by oxidative stress mechanisms. These findings also support the use of hESCs derived neurons as a platform for modeling neurodegenerative processes and the characterization of mitochondrial kinetics in disease, making these cells an optimal tool for further research in these fields.