China
Africa
Explore chapters and articles related to this topic
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).
Congenital Central Hypoventilation Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
At the molecular level, isolated and syndromic CCHS is mostly attributable to the polyalanine repeat expansion mutations (PARM) in the paired-like homeobox 2B (PHOX2B) gene on chromosome 4p13, with more severe disease being typically linked to nonpolyalanine repeat expansion mutations (NPARM) in PHOX2B. In rare cases, CCHS may be associated with mutations in several other genes, including GDNF (chromosome 5p13.2), RET (chromosome 10q11.21), ASCL1 (chromosome 12q23.2), and EDN3 (chromosome 20q13.32) [1].
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).
Novel targeted strategies to overcome resistance in small-cell lung cancer: focus on PARP inhibitors and rovalpituzumab tesirine
Published in Expert Review of Anticancer Therapy, 2019
Robin Van Den Borg, Alessandro Leonetti, Marcello Tiseo, Elisa Giovannetti, Godefridus J. Peters
Rova-T is injected intravenously and is an antibody-drug conjugate made of a humanized monoclonal antibody (SC16) directed against DLL3 that acts by attacking a DNA-damaging pyrrolobenzodiazepine dimer toxin SC-DR002 (D6.5) in DLL3-positive tumour cells. Since SCLC is frequently characterized by high expression of DLL3, Rova-T has selectivity against these tumours, by delivering and thus internalizing the toxin only in DLL3-expressing cells [97–99]. In humans, DLL3 is important for promoting neurogenesis and inhibiting gliogenesis in the human brain [100], and it is a crucial inhibitor of Notch pathway [100,101]. Importantly, Notch pathway activation shows opposite effects in SCLC and NSCLC, acting as a tumour suppressor as well as a tumour promoter, respectively [102]. The seminal study by George and colleagues [3] investigated mutations in 110 SCLC tumours via genome sequencing. Inactivating mutations were documented in NOTCH1, and in the majority of tumours (53/69, 77%) high levels of ASCL1 were found. ASCL1 is a lineage oncogene of neuroendocrine cells and can be inhibited by an active Notch signalling pathway [3]. This suggests that SCLC tumours commonly have a suppressed Notch signalling pathway, part of which can be accounted for high DLL3 expression.
Mnb/Dyrk1A orchestrates a transcriptional network at the transition from self-renewing neurogenic progenitors to postmitotic neuronal precursors
Published in Journal of Neurogenetics, 2018
Mirja N. Shaikh, Francisco J. Tejedor
Hes genes, the mammalian homologs of Dpn, are also activated in NPCs and downregulated in their neuronal progeny. There is abundant data showing that Hes TFs play an essential anti-differentiation role by regulating proliferation, specification and maintenance of NPCs (reviewed by Kageyama et al., 2008; Imayoshi & Kageyama, 2014). Thus, in many instances Hes and Ascl1 TFs play opposite roles in NPCs. Moreover, similarly to the effect of Dpn on Ase expression, Hes factors repress the expression of proneural genes, including Ascl1 (Hatakeyama et al., 2004; Imayoshi, Shimogori, Ohtsuka, & Kageyama, 2008). Noteworthy, Hes1 and Ascl1 are similarly downregulated before the division of mouse neurogenic progenitor cells. The daughter cell that self-renew as a NPC resumes Hes1 and Ascl1 expressions whereas the other daughter cell, which become a neuronal precursor, represses Hes1 and upregulates Ascl1 (Imayoshi et al., 2013).
The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy
Published in Renal Failure, 2019
Yinyin Chen, Liyu He, Yiya Yang, Ying Chen, Yanran Song, Xi Lu, Yumei Liang
Schneider et al. [8] has been demonstrated that fatty acid transport and uptake disorder in kidney is highly relevant for the renal lipid deposition. Renal lipid deposition is a crucial pathological change in ORN and inhibiting renal lipid deposition could slow the progression of ORN [9]. Storage of fatty acid as triglyceride (TG) requires the activation of fatty acids to long-chain acyl-CoAs (LC-CoA) by the enzyme acyl-CoA synthetase (ACSL). There are five known isoforms of ACSL (ACSL1, −3, −4, −5, −6), which vary in their tissue specificity and affinity for fatty acid substrates [10]. Long chain acyl-CoA synthetases-1, (ACSL1), is a key enzyme in the oxidative metabolism of fatty acids in mitochondria. ACSL1 not only could activate fatty acids for intracellular metabolism but are also involved in the regulation of uptake [11]. ACSL1 has been reported in fatty liver, skeletal muscle lipid degeneration, and ACSL is involved in lipid metabolism in different cells, either increasing lipid deposition or promoting lipid catabolism [12,13]. In kidney, inhibition of ASCL1 would result lipotoxic, finally expediting proximal tubule apoptosis [3,9]. Based on these data, we believe ACSL1 may be a key role in the progression of ORN. Interestingly, recent studies have emphasized the association of oxidative stress (ROS) with the pathogenesis of metabolic disorders in obesity [14]. ROS production was thought to be key importance in obesity-related kidney disease [15]. In addition, Trindade de Paula et al. confirmed that ROS levels were opposite to ACSL1 levels [16]. So, ROS production may be involved in the ORN through inhibiting the ACSL1 expression.