Implication of C/EBP¿ in the regulation of mitochondrial gene expression in in vitro models of Parkinson Disease

Trabajo presentado en el VII Congreso Internacional de Investigación e Innovación en Enfermedades Neurodegenerativas (CiiiEN), celebrado en Valencia (España) del 17 al 20 de septiembre de 2019.
Parkinson disease (PD) is the second most prevalent age-related neurodegenerative disorder after Alzheimer disease (1), resulting from degeneration of dopaminergic (DA) neurons in the ventral midbrain. To date, only symptomatic treatment is available; therefore, it is necessary to find new targets and treatments involved in the onset and progression of the disease. CCAAT/Enhancer Binding Protein ß (C/EBPß) is a transcription factor involved in numerous physiological as well as pathological conditions in the brain. Furthermore, C/EBPß depletion in in vitro and animal models of PD results in an amelioration of dopaminergic damage and glial activation (2), suggesting that this transcription factor could be a good therapeutic target for treatment of PD. Mitochondrial transcription factor A (TFAM) is a nuclear-encoded protein that is imported to this organelle and binds mitochondrial DNA (mtDNA) to regulate mitochondrial transcription initiation and mtDNA copy number. Furthermore, TFAM has a non-specific mtDNA binding activity that may have a structural role for genome packaging (3). It has been shown that TFAM has an important role in several neurodegenerative disorders (Reviewed in (4)) including PD. To date, there is no evidence about C/EBPß implication on mitochondrial activity. In this work, we demonstrate that C/EBPß regulates the expression of several mitochondrial genes and, more specifically TFAM transcription.