Transcriptional and epigenetic mechanisms underlying astrocyte identity

in 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 ▲]

Cellular models as tools for the study of the role of alpha-synuclein in Parkinson's disease

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 ▲]

Prox1 is required for oligodendrocyte cell identity in adult neural stem cells of the subventricular zone

in Stem Cells (2016)

Molecular function of TRIM32 in adult neurogenesis and regulation of Parkinson's disease associated genes

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 ▲]

The neural stem cell fate determinant TRIM32 regulates complex behavioral traits

in Frontiers in Cellular Neuroscience (2015)