China
Africa
Explore chapters and articles related to this topic
CDK Inhibitors in Leukemia and Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Cyclin D1 is a multifunctional protein that plays a critical role not only as a partner of CDK4/6 (see above) in the regulation of the cell cycle (e.g., the G1/S transition) but also as a transcriptional regulator by modulating the activity of several transcriptional factors (e.g., STAT3) that are CDK-independent. This may explain why cyclin D1 is not only involved in cell cycle progression but also in cell growth and survival (25). Cyclin D1 binds to transcriptional factors STAT3 and NeuroD and inhibits their transcriptional activity, which may be related to the modulation of cell differentiation. Cyclin D1 also interacts with histone deacetylases and, in so doing, blocks access of transcriptional factors to the promoter and inhibits loading of initiation complex (26). Cyclin D1, as an oncogene, also plays an important role in carcinogenesis, probably by driving cells into the S phase and cooperating with various oncogenes (such as Myc and Ras) in malignant transformation. Rearrangement of the cyclin D1 locus and/or overexpression of cyclin D1 have been reported in many human tumors, particularly mantle cell lymphoma (27).
Islet Transplantation in Type 1 Diabetes: Stem Cell Research and Therapy
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
In addition to endocrine cells, pancreatic exocrine cells also transform into other mature somatic lineage via transdifferentiation. In studies performed in rodents, it has been reported that beta-cell neogenesis and proliferation occurs from acinar cells instead of ductal progenitor cells [67]. Three transcription factors PDX1, ngn-3, and Mafa could play a major role in transdifferentiation and beta-cell neogenesis from pancreatic exocrine cells [68]. Certain organs due to their structural, and embryonic origin-similarities, may also show transdifferentiation. For instance, liver and pancreas show responsiveness to glucose and expression of similar genetic transcription factors. They share characteristics, origin and their adjacent location is suggestive of the fact that liver cells are convincing extrapancreatic cells that can trans-differentiate into pancreatic β-cells and thus can be used to generate transplantable insulin-producing cells [69]. Both adult and fetal liver cells have successfully been transfected via viral agents and trans-differentiated into pancreatic β-like cells [70]. Virally mediated combined expression of Pdx1/VP16 with neuroD/NGN3 in human hepatoma cell line, HepG2 induces insulin production and improves glucose tolerance in diabetic mice [71].
Neurogenesis in the Adult and Aging Brain
Published in David R. Riddle, Brain Aging, 2007
David R. Riddle, Robin J. Lichtenwalner
Data on aging-related changes in the genesis of olfactory receptor neurons are limited and analysis of changes is complicated by the fact that the olfactory epithelium, by virtue of its exposed location within the nasal cavity, is uniquely vulnerable to damage from a variety of insults. There are substantial aging-related changes in the organization of the olfactory epithelium, including a decrease in the number of ORNs and patchy replacement of the sensory epithelium by respiratory epithelium (e.g., [66, 67]. It cannot be assumed, however, that loss of ORNs is the result of decreased genesis. A short report that noted decreased generation of ORNs in the olfactory epithelium of aged mice [68] was followed by a detailed study of Fisher-344 × Brown Norway rats from 7 to 32 months of age [69]. Significantly, in the latter study, the animals were maintained in a barrier facility to minimize the possible impact of rhinitis and other disease on the olfactory epithelium. Although the anterior olfactory epithelium exhibited evidence of degeneration and gross morphological changes, the posterior region was well preserved, and BrdU labeling demonstrated that progenitor cells were dividing and new ORNs were produced even in the oldest animals. The generation of new neurons in the olfactory epithelium still was significantly reduced in older individuals; the number of BrdU-labeled basal cells and immature (GAP43-positive) neurons was approximately 40% lower in 32-month-old rats compared to 7-monthold young adults. Other investigators demonstrated a similar decrease between young adulthood and middle age in Sprague Dawley rats [70]. In addition to such evidence for decreased proliferation of progenitor cells, expression of NeuroD, a basic helix-loop-helix transcription factor that is thought to function in neuronal differentiation, is reduced in the aged olfactory epithelium [71].
High levels of HDAC expression correlate with microglial aging
Published in Expert Opinion on Therapeutic Targets, 2022
Jaione Auzmendi-Iriarte, Leire Moreno-Cugnon, Ander Saenz-Antoñanzas, Daniela Grassi, Marian M de Pancorbo, Maria-Angeles Arevalo, Ian C Wood, Ander Matheu
Epigenetic mechanisms are crucial for a variety of processes related to aging, such as cellular and organismal senescence, genomic instability, and carcinogenesis [27]. Several studies have suggested the impact of classical HDACs on brain function and aging. Recent studies performed in rodent models have revealed that in the hippocampus classical HDAC expression [28,29] and activity [30] increase with age. HDAC1, 3, 5, and 7 are highly expressed in NSCs, whereas HDAC2 is more widespread in the brain [31,32]. Notably, the treatment of adult NSCs with HDAC inhibitors (HDACi) induces differentiation and upregulates neuronal-specific genes, such as NeuroD, Neurogenin 1, and Math1 [33], which indicates the relevance of classical HDAC activity in NSC maintenance. In the same line, HDAC1 [34], HDAC2 [35], HDAC3 [36], HDAC4 [37], and HDAC6 [38] play key roles in associative and spatial memory, learning, and synaptic plasticity. The impact of HDAC enzymes also extends to the maintenance of other cell types, such as microglia. HDAC1 and HDAC2 activities regulate microglial function during the development and neurodegeneration [39]. However, the role of HDACs in microglial aging remains unexplored. In this study, we characterize the expression of several HDACs in two models of microglial senescence in vitro and different mouse and human brain samples from individuals of different ages.
Developmental neurotoxicity of silver nanoparticles: the current state of knowledge and future directions
Published in Nanotoxicology, 2022
Lidia Strużyńska, Beata Dąbrowska-Bouta, Grzegorz Sulkowski
In vitro models that use embryonic neural stem cells (NSCs) from mouse (Yin et al. 2018), human, and rat fetuses (Liu et al. 2015), and primary organotypic mouse midbrain cultures (Weldon et al. 2018) have been developed to determine whether AgNPs are capable of causing developmental neurotoxicity. The data from in vitro studies demonstrate that AgNPs perturb cell-specific differentiation processes in neural progenitors and induce abnormal expression of neural ectoderm marker genes, such as Sox1, Sox3, Map2, NeuroD, Nestin, and Pax6, at concentrations below 0.1 μg/mL (Yin et al. 2018). However, as the complexity of the CNS is extremely high and its proper functioning depends on the multidirectional interactions of brain cells which are impossible to reproduce in culture, we believe that in vitro models of AgNPs neurotoxicity are not as useful as animal models, particularly the rodent models which are frequently used for this purpose. According to the reported data, despite different time scales, the sequence of key events in brain development and maturation is largely consistent between humans and rodents and similarities in regional vulnerability to brain injuries can be observed (Semple et al. 2013).
Acetylation and insulin resistance: a focus on metabolic and mitogenic cascades of insulin signaling
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Solaleh Emamgholipour, Reyhane Ebrahimi, Alireza Bahiraee, Farshad Niazpour, Reza Meshkani
Mutations in HNF1A, -4A, -1B, IPF1/PDX1, and NEUROD1 genes as transcription factors have been reported to affect IR related disorders through modifying the function of HATs and HDACs. For instance, HNF1α stimulates transcription through applying the general transcription machinery and also the chromatin remodeling of promoter areas. The latter recruits HATs, which lead to histone acetylation and induction of the expression of GLUT2 and pyruvate kinase in β-cells [153,154]. However, in the presence of a specific missense mutation, R263L in the HNF1A gene, the affinity for p300 is reduced [155]. Furthermore, Pdx1, which regulates glucose-mediated insulin expression, needs the involvement of p300 as a HAT to acetylate histone H4 at the promoter of the insulin gene [156–158]. Interestingly, a lower level of glucose reduces the expression of insulin as a result of HDAC1 and 2 recruitment by Pdx1 [159]. Several mutations of the PDX1 gene in association with both p300 and DNA have been reported to have a crucial rule in the development of IR. Moreover, the NEUROD gene, which produces a key factor in developing the pancreas and controlling the expression of insulin, may also be mutated and lead to the production of a truncated protein and predisposition to IR. This mutation has been demonstrated to be the reason for the lack of binding of NEUROD to P300/CBP [160].