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   NF-κB and TNF Affect the Astrocytic Differentiation from Neural Stem CellsGrandbarbe, Luc  ; Michelucci, Alessandro ; Heuschling, Paul et alin Cells (2021) The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells ... [more ▼] The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells (NPCs). Here, we provide evidence that the NF-κB pathway plays also a fundamental role during the differentiation of NPCs into astrocytes. First, we show that the NF-κB pathway is essential to initiate astrocytic differentiation as its early inhibition induces NPC apoptosis and impedes their differentiation. Second, we demonstrate that persistent NF-κB activation affects NPC-derived astrocyte differentiation. Tumor necrosis factor (TNF)-treated NPCs show NF-κB activation, maintain their multipotential and proliferation properties, display persistent expression of immature markers and inhibit astrocyte markers. Third, we analyze the effect of NF-κB activation on the main known astrocytic differentiation pathways, such as NOTCH and JAK-STAT. Our findings suggest that the NF-κB pathway plays a dual fundamental role during NPC differentiation into astrocytes: it promotes astrocyte specification, but its persistent activation impedes their differentiation. [less ▲] Detailed reference viewed: 33 (4 UL)Transcriptional and epigenetic mechanisms underlying astrocyte identityPavlou, Maria Angeliki ; Grandbarbe, Luc ; et alin Progress in Neurobiology (2018) Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their ... [more ▼] Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their transition towards reactive astrocytes to their ability to undergo reprogramming, thereby revealing their potential to retain latent features of neural progenitor cells. We propose that the mechanisms underlying reactive astrogliosis or astrocyte reprogramming provide an opportunity for initiating neuronal regeneration, a process that is notably reduced in the mammalian nervous system throughout evolution. Conversely, this plasticity may also affect normal astrocytic functions resulting in pathologies ranging from neurodevelopmental disorders to neurodegenerative diseases and brain tumors. We postulate that epigenetic mechanisms linking extrinsic cues and intrinsic transcriptional programs are key factors to maintain astrocyte identity and function, and critically, to control the balance of regenerative and degenerative activity. Here, we will review the main evidences supporting this concept. We propose that unravelling the epigenetic and transcriptional mechanisms underlying the acquisition of astrocyte identity and plasticity, as well as understanding how these processes are modulated by the local microenvironment under specific threatening or pathological conditions, may pave the way to new therapeutic avenues for several neurological disorders including neurodegenerative diseases and brain tumors of astrocytic lineage. [less ▲] Detailed reference viewed: 162 (11 UL) Nuclear localization and phosphorylation modulate pathological effects of Alpha-Synuclein; ; et al in Human Molecular Genetics (2018) Detailed reference viewed: 162 (8 UL)Cellular models as tools for the study of the role of alpha-synuclein in Parkinson's diseasePavlou, Maria Angeliki ; ; in Experimental Neurology (2017) Neurodegenerative diseases are highly debilitating conditions characterised primarily by progressive neuronal loss and impairment of the nervous system. Parkinson's disease (PD) is one of the most common ... [more ▼] Neurodegenerative diseases are highly debilitating conditions characterised primarily by progressive neuronal loss and impairment of the nervous system. Parkinson's disease (PD) is one of the most common of these disorders, affecting 1-2% of the population above the age of 65. Although the underlying mechanisms of PD have been extensively studied, we still lack a full understanding of the molecular underpinnings of the disease. Thus, the in vitro and in vivo models currently used are able to only partially recapitulate the typical phenotypes of the disease. Here, we review various cell culture models currently used to study the molecular basis of PD, with a focus on alpha-synuclein-associated molecular pathologies. We also discuss how different cell models may constitute powerful tools for high-throughput screening of molecules capable of modulating alpha-synuclein toxicity. [less ▲] Detailed reference viewed: 92 (3 UL)Epigenetics in Parkinson's DiseasePavlou, Maria Angeliki ; in Neuroepigenomics in Aging and Disease (2017) Parkinson's disease (PD) is a highly complex neurodegenerative disorder with a multifactorial origin. Although several cellular mechanisms and genes have been implicated in the onset and progression of ... [more ▼] Parkinson's disease (PD) is a highly complex neurodegenerative disorder with a multifactorial origin. Although several cellular mechanisms and genes have been implicated in the onset and progression of the disease, the precise molecular underpinnings of the disease remain unclear. In this context, epigenetic modulation of gene expression by environmental factors is emerging as an important mechanism in PD and in other neurodegenerative disorders. Thus, epigenetic mechanisms, such as DNA methylation, histone modifications and altered microRNA expression, have been under intense investigation due to their possible involvement in PD. Epigenetic modulation is responsible for inducing differential gene expression, a phenomenon which is essential throughout life in order to regulate multiple cellular responses such as development, cellular fate commitment and adaptation to the environment. Disturbances of a balanced gene expression can, therefore, have detrimental effects. Environmental factors can challenge the establishment and maintenance of epigenetic modifications and could thereby fill the gap in our further understanding of origin and/or progression of neurodegenerative diseases. In this chapter, we focus on the role of epigenetics in PD. [less ▲] Detailed reference viewed: 100 (2 UL)Expression of the Parkinson’s Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32Pavlou, Maria Angeliki ; Colombo, Nicolo ; et alin Molecular Neurobiology (2016) Detailed reference viewed: 262 (15 UL)Prox1 is required for oligodendrocyte cell identity in adult neural stem cells of the subventricular zone; ; et al in Stem Cells (2016) Detailed reference viewed: 310 (10 UL)Molecular function of TRIM32 in adult neurogenesis and regulation of Parkinson's disease associated genesPavlou, Maria Angeliki Doctoral thesis (2015) In the adult brain, neurogenesis is restricted in two brain regions: i) the subventricular zone (SVZ) of the lateral ventricles and ii) the dentate gyrus of the hippocampus. Adult neural stem cells of the ... [more ▼] In the adult brain, neurogenesis is restricted in two brain regions: i) the subventricular zone (SVZ) of the lateral ventricles and ii) the dentate gyrus of the hippocampus. Adult neural stem cells of the SVZ continuously generate new neurons for the olfactory bulb (OB). The fate commitment of these cells is regulated by cell fate determining proteins. Here, we aim to investigate the role of TRIM32 during the process of adult neurogenesis and understand its function in the mammalian system. In addition, we aim to identify the role of TRIM32 in transcriptional regulation of Parkinson’s disease (PD) associated genes. We focus on alpha synuclein, a gene which is also implicated in neuronal dysfunction, death and proliferation of neural stem cells. Acquiring more knowledge about the regulation of this gene may be critical for PD pathogenesis and will allow us to come to a closer understanding of the disease. [less ▲] Detailed reference viewed: 207 (21 UL)Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progressionLe Grand, Jaclyn Nicole ; Gonzalez Cano, Laura ; Pavlou, Maria Angeliki et alin Cellular and Molecular Life Sciences (2015) Detailed reference viewed: 393 (23 UL)The neural stem cell fate determinant TRIM32 regulates complex behavioral traitsHillje, Anna-Lena ; ; Pavlou, Maria Angeliki et alin Frontiers in Cellular Neuroscience (2015) Detailed reference viewed: 259 (22 UL)TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiationHillje, Anna-Lena ; Pavlou, Maria Angeliki ; et alin Cell Death and Disease (2013) Detailed reference viewed: 232 (12 UL) |
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