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Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ritika Raghavan, Robert Juniewicz, Maharaib Syed, Michael Lin, Peng Jiang
With advances in cellular reprogramming research, the direct reprogramming approach aims to use transcription factors, small molecules, microRNAs, and epigenetic modifiers or a combination of them to convert somatic cells, such as skin fibroblasts, directly to functional neurons and glia (18–20). The original study that first reported the direct reprogramming of terminally differentiated mouse fibroblasts into induced neurons used three neuronal transcription factors: Brn2, Ascl1, and Myt1L, known as the “BAM” factors. The fibroblasts were observed to drastically change in morphology into and become neuronal cells without cell division through a transient stage (21). Along with the addition of NeuroD1, these BAM factors were also able to convert human fibroblasts to functional neurons (22). This method retains the advantages of the accelerated differentiation approach along with the added advantage of not having to use PSCs as the starting cells in culture as somatic cells are readily available (23).
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Activation of RAR and PPAR by RA is crucial for induction of neuronal differentiation, and various target genes have been reported to be involved in this process (25,26). RA, through its effectors, directly regulates expression of subset of homeotic genes (Hox) Hoxa-1, Hoxb-2, and Wnt-1 (27). These master control genes specify the body plan and regulate the development and morphogenesis of higher organisms. In addition, RA also indirectly regulates achaete-scute family bHLH transcription factor 1 gene (ASCL1), Neurogenin 1 (NEUROG1), neuronal differentiation 1 (NeuroD1), N-cadherin/cadherin 2 (CDH2), and pre-B-cell leukemia transcription factors or PBX homeobox genes (Pbx) (7).
Endocrinology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Mehul Dattani, Catherine Peters
MODY affects 1–2% of people with diabetes, and is inherited in an autosomal dominant manner. Six genes have been identified to date including HNF1A, Glucokinase, HNF1B (including renal cysts and diabetes), HNF4A, IPF1, and NEUROD1.
The impact of leptin and its receptor polymorphisms on type 1 diabetes in a population of northwest Iran
Published in Annals of Human Biology, 2022
Parviz Azimnasab-sorkhabi, Maryam Soltani-asl, José Roberto Kfoury, Petra Algenstaedt, Hakan Farzin Mehmetzade, Yashar Hashemi Aghdam
Genetic polymorphisms have the potential to support or even cause phenotypic diversities among people such as disease risk and medication responses. Characterisation of genetic polymorphisms that regulate gene expression and protein function may assist in the recognition of various variants (Jin et al. 2018). Several studies have revealed associations between polymorphisms and diabetes in different populations including the Iranian population. For instance, recently, it has been shown that in the Iranian population NeuroD1 Ala45Thr polymorphism is significantly associated with T1D (Soltani Asl et al., 2020). Importantly, leptin (LEP) and leptin receptor (LEPR) genes are potential candidates to contribute to the pathophysiology of diabetes, obesity, metabolic syndrome, and cancer (Nesrine et al. 2018; Cheng et al. 2020). The LEP is an adipocyte-derived peptide hormone and plays several important roles in human physiology (Hussain et al. 2015; Yan et al. 2016). Therefore, the LEP G2548A and LEPR Q223R polymorphisms are potential targets to further studies at the genetic level to expand our knowledge regarding involved mechanisms in diabetes.
Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility
Published in Stress, 2018
Julia K Gjerstad, Stafford L Lightman, Francesca Spiga
Genomic mechanisms. CRH-induced activation of the cAMP/PKA pathway results in phosphorylation of CREB and subsequent transcription of POMC. In addition, CRH also activates the MAPK pathway (Kovalovsky et al., 2002) resulting in activation of the orphan nuclear receptor Nur77 (Philips et al., 1997). The binding of Nur77 to the NurRE within the POMC promoter is known to enhance pCREB-mediated gene transcription (Phillips et al., 1997). CORT mediates negative feedback by inhibiting ACTH synthesis through a mechanism that requires binding of activated GR to an nGRE within the POMC promoter (Drouin et al., 1989a, 1989b). In addition, GR can inhibit Nur77-induced POMC transcription through a protein–protein interaction mechanism (Martens et al., 2005; Philips et al., 1997). A recent study suggests an involvement of NeuroD1 in regulating POMC transcription (Parvin et al., 2017). In the absence of CORT, NeuroD1 interacts with the E-box on the POMC promoter and activates transcription (Poulin et al., 1997). Increased CORT concentration causes a repression of NeuroD1 expression, and hence less activation of POMC transcription (Parvin et al., 2017).
Targeting the Wnt/β-catenin pathway in neurodegenerative diseases: recent approaches and current challenges
Published in Expert Opinion on Drug Discovery, 2020
Annalucia Serafino, Daniela Giovannini, Simona Rossi, Mauro Cozzolino
Among the Wnt target genes, numerous are those related to neurogenesis as well as to neuron survival, maintenance, and plasticity in the adult brain. We briefly describe below some of those that are upregulated by the Wnt signaling cascade. The CCND1 gene encodes for the cyclin D1 protein, which regulates cell cycle progression and neuronal function, and promotes neuron differentiation and neurogenesis [59]. The NEUROD1 (neuronal differentiation 1) gene encodes for a proneural transcription factor essential for the development of the CNS, and particularly for the generation of granule cells in the hippocampus and cerebellum [60]. Other Wnt target genes that are up-regulated by Wnt signaling are those encoding for survivin, whose expression seems to be crucial for restoring neural progenitor cells (NPCs) proliferation by the neurogenic niche in the aged brain [61], and for Mmp9 (Matrix metalloproteinase 9), that affects embryonic and adult neurogenesis and neuron plasticity [62,63]. The β-catenin/LEF1 complex appears also to enhance the expression of CACNA1 G (calcium voltage-gated channel subunit alpha1 G) gene, that encodes for Cav3.1, the predominant T-type channel subunit present in mature thalamic neurons [64], and to directly regulate the promoter of NEUROGENIN 1, a gene implicated in cortical neuronal differentiation [65]. Moreover, β-catenin directly binds to the promoter region of NURR1 gene [66], which encodes the Nurr1 protein essential for both survival and final differentiation of ventral mesencephalic dopaminergic precursor neurons [67]. Finally, Wnt signaling seems to directly activate the BDNF gene, encoding for the brain-derived neurotrophic factor that plays important roles in neuronal survival, neurogenesis, differentiation, and neurite growth throughout the CNS [68].