1. C/EBPβ Regulates TFAM Expression, Mitochondrial Function and Autophagy in Cellular Models of Parkinson's Disease.
- Author
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Sierra-Magro, Ana, Bartolome, Fernando, Lozano-Muñoz, David, Alarcón-Gil, Jesús, Gine, Elena, Sanz-SanCristobal, Marina, Alonso-Gil, Sandra, Cortes-Canteli, Marta, Carro, Eva, Pérez-Castillo, Ana, and Morales-García, José A.
- Subjects
PARKINSON'S disease ,CELL physiology ,MITOCHONDRIA ,SUBSTANTIA nigra ,TRANSCRIPTION factors ,DOPAMINERGIC neurons - Abstract
Parkinson's disease (PD) is a neurodegenerative disorder that results from the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Since there are only symptomatic treatments available, new cellular and molecular targets involved in the onset and progression of this disease are needed to develop effective treatments. CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor levels are altered in patients with a variety of neurodegenerative diseases, suggesting that it may be a good therapeutic target for the treatment of PD. A list of genes involved in PD that can be regulated by C/EBPβ was generated by the combination of genetic and in silico data, the mitochondrial transcription factor A (TFAM) being among them. In this paper, we observed that C/EBPβ overexpression increased TFAM promoter activity. However, downregulation of C/EBPβ in different PD/neuroinflammation cellular models produced an increase in TFAM levels, together with other mitochondrial markers. This led us to propose an accumulation of non-functional mitochondria possibly due to the alteration of their autophagic degradation in the absence of C/EBPβ. Then, we concluded that C/EBPβ is not only involved in harmful processes occurring in PD, such as inflammation, but is also implicated in mitochondrial function and autophagy in PD-like conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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