CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson's disease.
Jose Ángel Morales-GarcíaElena GineElena Hernandez-EncinasDiana Aguilar-MoranteAna Sierra-MagroMarina Sanz-SanCristobalSandra Alonso-GilRaul Sanchez-LanzasJose G CastañoAngel SantosAna Pérez-CastilloPublished in: Scientific reports (2017)
The CCAAT/Enhancer binding protein β (C/EBPβ) is a transcription factor involved in numerous physiological as well as pathological conditions in the brain. However, little is known regarding its possible role in neurodegenerative disorders. We have previously shown that C/EBPβ regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have analyzed the effects of C/EBPβ interference in dopaminergic cell death and glial activation in the 6-hydroxydopamine model of Parkinson's disease. Our results showed that lentivirus-mediated C/EBPβ deprivation conferred marked in vitro and in vivo neuroprotection of dopaminergic cells concomitant with a significant attenuation of the level of the inflammatory response and glial activation. Additionally, C/EBPβ interference diminished the induction of α-synuclein in the substantia nigra pars compacta of animals injected with 6-hydroxydopamine. Taking together, these results reveal an essential function for C/EBPβ in the pathways leading to inflammatory-mediated brain damage and suggest novel roles for C/EBPβ in neurodegenerative diseases, specifically in Parkinson's disease, opening the door for new therapeutic interventions.
Keyphrases
- binding protein
- brain injury
- transcription factor
- cell death
- inflammatory response
- cerebral ischemia
- subarachnoid hemorrhage
- oxidative stress
- neuropathic pain
- white matter
- cell cycle arrest
- induced apoptosis
- resting state
- poor prognosis
- signaling pathway
- cell proliferation
- multiple sclerosis
- lipopolysaccharide induced
- spinal cord
- physical activity
- radiation therapy
- functional connectivity
- dna binding
- endoplasmic reticulum stress