• The observation that mutations in more than 20 genes encoding for lysosomal proteins causes defects in skeletal growth in human suggests that lysosomal pathways play an important, yet unexplored, role during skeletogenesis. (ectsoc.org)
  • Autophagy is a process of engulfing one's own cytoplasmic proteins or organelles and coating them into vesicles, fusing with lysosomes to form autophagic lysosomes, and degrading the contents it encapsulates. (hindawi.com)
  • The hallmark of autophagy is the formation of autophagosomes, where lysosomes wrap cytoplasmic proteins or organelles and achieve self-renewal [ 4 ]. (hindawi.com)
  • They have shown that UVRAG function and autophagy are inactivated by oncogenes such as cellular Bcl-2 and oncogenic γ-herpesvirus-encoded Bcl-2 proteins, by the oncogenic BRAF kinase, and by genetic mutations that increase inflammation and cancer susceptibility and can also be hitchhiked by viruses for their efficient infection. (upenn.edu)
  • Multiple gene mutations have been identified and considered as important substrates for the development of MDS, such as RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements. (frontiersin.org)
  • Moreover, cells use autophagy to regulate the activity of specific signaling proteins, to prevent accumulation of damaged organelles or long-lived, aggregate-prone proteins, and to remove incoming threats such as intracellular pathogens. (invivogen.com)
  • Nonetheless, it is important to remember that these and other autophagy proteins also execute many non-autophagy functions. (invivogen.com)
  • However, autophagy can also be used to spatiotemporally regulate immune signaling pathways (e.g. by recycling activated proteins to limit cytokine production) and block inflammation (e.g. by removing damaged mitochondria before they can release harmful reactive oxygen species). (invivogen.com)
  • Interestingly, autophagy and its signaling proteins have been associated with inflammatory disorders, including Crohn's disease (CD), certain cancers, and autoimmune diseases such as sclerosis and systemic lupus erythematosus (SLE) 3 . (invivogen.com)
  • Biosynthesis and intracellular trafficking of secretory and lysosomal/vacuolar proteins, glycosylation and other post-translational protein modifications as determinants of protein structure and function, catalytic properties and physiological functions of proteases and glycosylation enzymes, proteolysis and its pathological and biotechnological relevance, recombinant expression of biotherapeutics in plants, plant membrane protein biochemistry. (boku.ac.at)
  • In mammals, transport of CREG to these compartments was shown to rely on the M6P receptor pathway as typical for soluble lysosomal proteins. (boku.ac.at)
  • We have demonstrated that ApoE4 competes with Transcriptional Factor EB (TFEB) for binding to the CLEAR DNA motifs, thus, hindering the transcription of three proteins crucial for lysosomal autophagy. (hhs.gov)
  • Now, importantly, we have identified a lead compound that binds to ApoE4 protein, obviating its interactions with CLEAR DNA and restoring the expression of three autophagy genes, that encode for production of p62, LC3B, and LAMP2 proteins. (hhs.gov)
  • Autophagy, the type II cell death, is a physiological mechanism involving degradation of intracellular damaged proteins and organelles into membrane vacuoles. (ijpsonline.com)
  • The contributors describe strategies for identifying and evaluating the biochemical and morphological changes that occur during apoptosis, autophagy, necrosis, and other forms of cell death, as well as for pinpointing the genes and proteins that may be involved. (cshlpress.com)
  • Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. (stanford.edu)
  • Dysregulation of maturation of lysosomal proteins as well as an accumulation of ubiquitinated proteins and widespread p62 deposition suggest that proteostasis is impaired. (synergy-munich.de)
  • TFEB coordinates the lysosomal proteins (the waste bins of our cells) and the genes involved in autophagy[3]. (longlonglife.org)
  • We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. (ox.ac.uk)
  • Small molecule GSK-3β inhibitors and GSK-3β knockdown using siRNA promote the expression of autophagy-related proteins. (mdpi.com)
  • Autophagy is an adaptive catabolic process by which cytoplasmic proteins and organelles are targeted to lysosomes for degradation [ 12 ]. (biomedcentral.com)
  • Overall, this study reveals the impact of cln5 -deficiency on gene expression in D. discoideum , provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease. (frontiersin.org)
  • The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. (nih.gov)
  • Autophagy selectively targets dysfunctional organelles, intracellular microbes, and pathogenic proteins, and deficiencies in these processes may lead to disease. (elsevierpure.com)
  • The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. (molcells.org)
  • More recently, the concept of lysosomal storage disease has been expanded to include deficiencies or defects in proteins necessary for the normal post-translational modification of lysosomal enzymes (which themselves are often glycoproteins), activator proteins, or proteins important for proper intracellular trafficking between the lysosome and other intracellular compartments. (medscape.com)
  • Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. (mdpi.com)
  • The main research interest of my laboratory is to understand the regulation and the role of the lysosomal-autophagy pathway in both physiological and disease processes. (ectsoc.org)
  • In particular, keeping in mind that the lysosomal-autophagy pathway is dynamically regulated in response to changes in the extracellular environment, my laboratory is exploring the hypothesis that the developmental regulation of this pathway is an important contributor to organismal development and growth. (ectsoc.org)
  • Currently, my laboratory is investigating the role of the lysosomal autophagy pathway during skeletal development and growth. (ectsoc.org)
  • The homeostasis of all eukaryotic cells depends on their "greening" ability to use a lysosomal pathway known as autophagy to degrade and recycle self-components. (upenn.edu)
  • Using a series of genetic, biochemical, molecular and cell biological, and computational approaches in model organisms from Drosophila to Zebrafish to mice, we have defined both canonical and non-degradative functions of UVRAG and the autophagy pathway in multiple endomembrane trafficking (Nat Cell Bio. (upenn.edu)
  • Autophagy, a highly regulated pathway, is entered by cells under various conditions including starvation, protein misfolding and oxidative stress. (mskcc.org)
  • Transcription factor EB (TFEB) has been shown to be the master regulatory of the autophagic-lysosomal pathway. (mskcc.org)
  • Inactivation of mTORC1 in this pathway thus leads to translocation of TFEB into the nucleus, where it initiates autophagic and lysosomal-related gene expression. (mskcc.org)
  • The classical autophagy pathway proceeds through a series of well-defined steps. (invivogen.com)
  • The classical autophagy pathway requires the concerted action of a set of evolutionarily conserved genes . (invivogen.com)
  • Gene set enrichment analysis revealed that the lipid metabolism pathway was suppressed in KDM6B-KO cells. (bvsalud.org)
  • Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. (ox.ac.uk)
  • These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation. (ox.ac.uk)
  • MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. (icr.ac.uk)
  • The lysosomal degradation pathway of autophagy plays a fundamental role in cellular, tissue, and organismal homeostasis and is mediated by evolutionarily conserved autophagy-related (ATG) genes. (elsevierpure.com)
  • Autophagy is a major cellular lysosomal degradation pathway of bulk material, and levels are known to fall with age. (ox.ac.uk)
  • Mammospheres express high ranges of lysosomal and oxidative phosphorylation genes In order to even further investigate molecular distinctions between mammospheres and adherently cultured cells, gene expression profiles had been in contrast, the results of the pathway enrichment analysis are summarized in Added file 4. (pkc-inhibitors.com)
  • Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. (nature.com)
  • Mutations in this gene increase lysosomal pH. (wikipedia.org)
  • More than 130 mutations in the ARSB gene have been found to cause mucopolysaccharidosis type VI (MPS VI). (medlineplus.gov)
  • Most of these mutations change single DNA building blocks (nucleotides) in the gene. (medlineplus.gov)
  • Garrido E, Cormand B, Hopwood JJ, Chabas A, Grinberg D, Vilageliu L. Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene. (medlineplus.gov)
  • There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. (nature.com)
  • Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. (nature.com)
  • MDS was found to be related to genetic mutations or epigenetic modifications, which lead to abnormal autophagy, apoptosis of mature cells, chromosomal abnormalities, and a high level of inflammation in the bone marrow microenvironment ( 4 - 8 ). (frontiersin.org)
  • Although the utility of these prognostic assessment systems has been confirmed in clinical practice, they do not take gene mutations into account ( 13 ). (frontiersin.org)
  • Kinase-activating mutations in the LRRK2 gene are the most frequent cause of inherited PD (reviewed in Schneider and Alcalay, 2020 ). (alzforum.org)
  • While most of the CLN genes have been studied, the precise cellular mechanisms impacted by CLN gene mutations remain elusive. (frontiersin.org)
  • It is caused by mutations in the CTNS gene, which encodes the lysosomal transporter cystinosin, resulting in intralysosomal accumulation of cystine. (uu.nl)
  • Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. (nih.gov)
  • Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s). (nih.gov)
  • Definitive etiological links exist between mutations in genes that control autophagy and human disease, especially neurodegenerative, inflammatory disorders and cancer. (elsevierpure.com)
  • Age of onset and clinical manifestations may vary widely among patients with a given lysosomal storage disease, and significant phenotypic heterogeneity between family members carrying identical mutations has been reported. (medscape.com)
  • Results Irinotecan dose-dependently induced lipid accumulation and pro-inflammatory gene expression in hepatocytes. (bmj.com)
  • ERK inhibition prevented irinotecan-induced pro-inflammatory gene expression but had only a slight effect on lipid accumulation. (bmj.com)
  • Re-acidification of lysosomal pH abolished irinotecan-induced autophagy impairment and lipid accumulation. (bmj.com)
  • Studies have shown that Tubeimoside-I (TBM), as a new lethal autophagy lysosomal inducer, can induce autophagy accumulation and may enhance the therapeutic effect of chemotherapeutic drugs on cervical cancer [ 8 ]. (hindawi.com)
  • Additionally, defective autophagy has been implicated in neurologic disorders characterized by accumulation of protein aggregates, including Parkinson's disease. (invivogen.com)
  • The absence of inclusions could be due to highly active autophagy that prevents the accumulation of exogenous alpha-synuclein. (michaeljfox.org)
  • The researchers found that loss of autophagy caused accumulation of alpha-synuclein protein in the brain. (michaeljfox.org)
  • Inhibition of autophagy via bafilomycin A1 aggravated H 2 O 2 -induced reactive oxygen species (ROS) accumulation and apoptosis in MAC-T cells. (biomedcentral.com)
  • Overexpression of TFEB activated autophagy and attenuated H 2 O 2 -induced ROS accumulation. (biomedcentral.com)
  • Our results indicate that activation of TFEB mediated autophagy alleviates H 2 O 2 -induced oxidative damage by reducing ROS accumulation and inhibiting caspase-dependent apoptosis. (biomedcentral.com)
  • of cystinosin is associated with disrupted autophagy dynamics, accumulation of distorted mitochondria, and increased oxidative stress, leading to abnormal proliferation and dysfunction of kidney cells. (uu.nl)
  • Lysosomal storage diseases describe a heterogeneous group of dozens of rare inherited disorders characterized by the accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities. (medscape.com)
  • However, irinotecan also induced an impairment of the autophagic flux mediated by alkalisation of lysosomal pH. (bmj.com)
  • Furthermore, irinotecan-treated patients revealed higher hepatic ERK activity, expression of pro-inflammatory genes and markers indicative for a shift to peroxisomal fatty acid oxidation and an impaired autophagic flux. (bmj.com)
  • Due to increasing reports implicating autophagy in the clearance of Tau aggregates in Alzheimer's disease and in the promotion of tumor progression in various types of cancer, as well as in studies demonstrating the downsides of long-term mTOR, our lab investigates small molecules as autophagic inducers to promote autophagic flux through mTOR independent pathways. (mskcc.org)
  • Thus, a loss of function of TMEM106B may enhance the risk for GRN‐associated FTLD by reduced protein turnover in the lysosomal/autophagic system. (synergy-munich.de)
  • Upon autophagy induction microtubule-associated protein light chain 3 (LC3) can specifically target autophagic membranes to form autophagosomes [12]. (crispr-reagents.com)
  • Autophagy also plays an important role in preventing cisplatin-induced apoptosis of cervical cancer cells, suggesting that inhibition of autophagy may improve cisplatin chemotherapy [ 10 ]. (hindawi.com)
  • Inhibition of this protein sequesters HLH-30, a transcription factor that regulates autophagy, within the nucleus and promotes its action on DNA[2]. (longlonglife.org)
  • It would seem that the effects resulting from the inhibition of XPO1 are also preserved in humans, since analyses performed on HeLa cells showed that the concentration of TFEB in the nucleus as well as autophagy were increased following this inhibition[1]. (longlonglife.org)
  • It had been observed that inhibition of ATG4A had no effect on cell viability underneath adherent culture circumstances illustrating that ATG4A will not be an essen tial gene for that bulk of SUM 149 cells. (pkc-inhibitors.com)
  • Interestingly, both events are dramatically enhanced in AD patients who inherit the Alzheimer gene from both parents (genotype ApoE4,4). (hhs.gov)
  • Interestingly, autophagy suppression resulted in a late and moderate loss of midbrain dopamine neurons in the substantia nigra, accompanied by impairment of locomotor activity. (michaeljfox.org)
  • Interestingly, autophagy levels were diminished in CD8(+) T cells from aged mice. (ox.ac.uk)
  • Interestingly, strongest enrichment of up regulated genes was noticed for lysosome connected genes and genes concerned in oxidative phosphorylation indicating a requirement of lysosomal action and power generation underneath sphere forming disorders. (pkc-inhibitors.com)
  • Conditions such as MPS VI that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. (medlineplus.gov)
  • Half a century ago, Christian de Duve coined the term "autophagy" (literally, "self-eating" in Greek) to describe a process where the cell digests its cytoplasmic materials within lysosomes 1 . (nature.com)
  • These results establish that CREG is a lysosomal protein that undergoes proteolytic maturation in the course of its biosynthesis, carries the M6P recognition marker and depends on the interaction with M6P receptors for efficient delivery to lysosomes. (boku.ac.at)
  • Degradation of macromolecules delivered to lysosomes by processes such as autophagy or endocytosis is crucial for cellular function. (stanford.edu)
  • Bafilomycin A1 (Baf A1) a particular inhibitor from the vacuolar-type H+-ATPase helps prevent autophagy at a past due stage by inhibiting the fusion between autophagosomes and lysosomes. (crispr-reagents.com)
  • However, these experimental results do not directly demonstrate that defects in autophagy contribute to pathogenesis of human diseases. (nature.com)
  • Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). (frontiersin.org)
  • However, with the development of gene expression profile and new high-throughput technology, the understanding of the pathogenesis of MDS is getting further and better. (frontiersin.org)
  • The role of bisphenol A in autophagy modulation involved in the pathogenesis of diseases is still debatable. (mendeley.com)
  • dysfunction of autophagy predisposes to the pathogenesis of PD in dopamine neurons. (michaeljfox.org)
  • Our study exhibited that and play pivotal functions in the molecular pathogenesis of MM. This is usually the first statement describing the possible functions of in myelomagenesis and its potential role as a SU 11654 therapeutic target in MM. gene promotes tumorigenesis through constant NAD resynthesis to provide adequate energy for rapidly proliferating malignancy cells [9]. (forgetmenotinitiative.org)
  • Our results offer a even more unique understanding of the jobs of and genes in the molecular pathogenesis of MM. MATERIALS AND METHODS Cell collection The myeloma cell collection RPMI 8226 was purchased from the American Type Culture Collection (ATCC, USA). (forgetmenotinitiative.org)
  • Autophagy is a catabolic process involved in cellular defense and the stress response ( 15 ) and plays an essential role in the differentiation of hematopoietic cells. (frontiersin.org)
  • Autophagy has been extensively linked to innate immune signaling pathways-for example, during cellular responses to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). (invivogen.com)
  • In our search for potentially tumour-suppressive M6P/IGF2R interaction partners, we identified an essentially uncharacterized M6P-modified protein previously named Cellular Repressor of E1A-stimulated Genes (CREG). (boku.ac.at)
  • Autophagy and apoptosis are two forms of programmed cell death, which are essential for cellular homeostasis. (ijpsonline.com)
  • Autophagy, regarded generally as a protective mechanism that maintains cell viability by recycling unwanted and damaged cellular constituents, is nevertheless subject to dysregulation having detrimental effects for the cell. (oncotarget.com)
  • Autophagy is a regulated lysosomal degradation which has the capacity to clear large protein/lipid complexes, toxic aggregates and cellular organelles. (michaeljfox.org)
  • Autophagy is a conserved biological process that recycles damaged cell compounds, allowing the cell to fight cellular stress and cell death. (longlonglife.org)
  • Surprisingly, the post-natal induction of chondrocyte autophagy is mediated by the FGF signaling, demonstrating that autophagy is a developmentally regulated process necessary for bone growth. (ectsoc.org)
  • Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I. (nih.gov)
  • The induction of autophagy is a mechanism of secondary resistance to various anticancer treatments. (mdpi.com)
  • RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. (icr.ac.uk)
  • Induction of autophagy is tightly regulated at the transcriptional level and involves the master regulator, transcription factor EB (TFEB). (biomedcentral.com)
  • therefore the improved degrees of autophagosomes can symbolize either the induction of autophagy or the blockage from the downstream lysosomal control of the autophagosomes or both [18]. (crispr-reagents.com)
  • Lysosomal storage diseases are generally classified by the accumulated substrate and include the sphingolipidoses, oligosaccharidoses, mucolipidoses, mucopolysaccharidoses (MPSs), lipoprotein storage disorders, lysosomal transport defects, neuronal ceroid lipofuscinoses and others. (medscape.com)
  • TFEB links autophagy to lysosomal biogenesis. (ectsoc.org)
  • The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans, Nat Commun. (longlonglife.org)
  • Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). (ox.ac.uk)
  • Transcription factor EB (TFEB)-mediated autophagy is an important cytoprotective mechanism against oxidative stress. (biomedcentral.com)
  • However, effects of TFEB-mediated autophagy on the oxidative stress of bovine mammary epithelial cells remain unknown. (biomedcentral.com)
  • Therefore, the main aim of the study was to investigate the role of TFEB-mediated autophagy in bovine mammary epithelial cells experiencing oxidative stress. (biomedcentral.com)
  • Thus, TFEB-mediated autophagy in bovine mammary epithelial cells might play a positive role in response to oxidative stress. (biomedcentral.com)
  • In the next years my lab will focus on determining the molecular mechanisms by which FGF signaling pathways control autophagy in chondrocytes and osteoblasts and on the identification of the physiological roles of autophagy in bone and cartilage. (ectsoc.org)
  • However, the prognostic role of autophagy genes in cervical cancer is still unclear. (hindawi.com)
  • Many studies have demonstrated the important role of autophagy in cervical cancer. (hindawi.com)
  • However, while these studies have revealed the role of autophagy in the occurrence and development of cervical cancer and its relationship with various tumor drugs, few studies have examined the prognostic role of autophagy in cervical cancer. (hindawi.com)
  • In this investigation, the role of autophagy and apoptosis in Solanum nigrum fruit extract-induced cytotoxicity in MDA-MB-468, a triple negative breast cancer cell line was studied. (ijpsonline.com)
  • A few research studies have shown bisphenol Ainduced adverse effects to be associated with autophagy dysregulation, while a few have shown the activation of autophagy to be mediated by bisphenol A. Such contrasting views make the subject more interesting and debatable. (mendeley.com)
  • In addition, we plan to explore the therapeutic potential of the pharmacological modulation of autophagy as treatment of skeletal dwarfisms. (ectsoc.org)
  • A proper understanding of the role of bisphenol A in the modulation of autophagy may be important for future treatment and drug discovery. (mendeley.com)
  • However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. (nature.com)
  • This review focuses on the role of macroautophagy (hereafter referred to as autophagy) in human diseases. (nature.com)
  • Thus, it has become particularly important to understand the genetic basis of putative human autophagy-related diseases. (nature.com)
  • Indeed, genome-wide studies have identified disease-associated loci and genes in many human diseases. (nature.com)
  • Table 1 summarizes the association between genetic variants of autophagy-related genes and selected human diseases. (nature.com)
  • Dr. Pasqualina Colella is a scientist with extensive expertise in cell therapy and gene therapy approaches for the treatment of inherited diseases. (stanford.edu)
  • She is currently Research Scientist at Stanford University, where she is developing innovative cell therapy approaches to address neuropathic lysosomal storage diseases (LSDs) using hematopoietic stem cell transplantation (HSCT) and genome editing. (stanford.edu)
  • Inhibiting the nuclear export protein XPO-1 in humans could be applied in therapy, against diseases characterized by lysosomal abnormalities and age-related autophagy abnormalities. (longlonglife.org)
  • The NCLs, commonly referred to as Batten disease, are a family of neurodegenerative lysosomal storage diseases that affect all ages and ethnicities globally. (frontiersin.org)
  • Classically, lysosomal storage diseases encompassed only enzyme deficiencies of the lysosomal hydrolases. (medscape.com)
  • More than 50 lysosomal storage diseases have been described, some of which are discussed in this article. (medscape.com)
  • Thus far, ERT has been largely unsuccessful in improving central nervous system manifestations of the lysosomal storage diseases, putatively due to difficulty in penetrating the blood-brain barrier. (medscape.com)
  • This has led to active clinical trials evaluating the safety and efficacy of intrathecal enzyme delivery in several lysosomal storage diseases (see www.ClinicalTrials.gov ). (medscape.com)
  • Accumulated data indicate that hematopoietic stem cell transplantation may be effective under optimal conditions in preventing the progression of central nervous system symptoms in neuronopathic forms of lysosomal storage diseases (such as Krabbe disease), including some of the mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses, and lipidoses as well as peroxisome disorders such as X-linked adrenoleukodystrophy. (medscape.com)
  • The availability of both ERT and hematopoietic stem cell transplantation has prompted ongoing consideration of newborn screening efforts to diagnose lysosomal storage diseases. (medscape.com)
  • Accumulated data indicate that hematopoietic stem cell transplantation may be effective under optimal conditions in preventing the progression of central nervous system symptoms in neuronopathic forms of lysosomal storage diseases, including some of the mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses, and lipidoses. (medscape.com)
  • This process is closely related to the carcinogenesis, with cancer cells relying on systemic autophagy in their cytoplasm and in the host to sustain growth [ 6 ], providing the necessary nutrients and raw materials [ 7 ]. (hindawi.com)
  • Autophagy, often referred to as macroautophagy, serves to recycle large chunks of cytoplasm as a source of nutrients, which enables cells to maintain macromolecular synthesis and energy homeostasis during starvation and other stressful conditions. (invivogen.com)
  • During starvation or certain forms of stress, cells use autophagy to digest and recycle large, non-specific parts of their cytoplasm. (invivogen.com)
  • During autophagy, phagophores capture portions of cytoplasm and form double-membrane autophagosomes to deliver cargo for lysosomal degradation. (rupress.org)
  • To test this, we will establish conditional knock-out mice in which an essential autophagy gene, Atg7, is deleted specifically in dopamine neurons. (michaeljfox.org)
  • We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. (ox.ac.uk)
  • Mice lacking the autophagy gene Atg7 in T cells failed to establish CD8(+) T cell memory to influenza and MCMV infection. (ox.ac.uk)
  • Liang lab has identified and studied the mammalian essential autophagy protein, UV irradiation resistance associated gene (UVRAG), which functions in and beyond autophagy and has emerging significance in cancer research. (upenn.edu)
  • Furthermore, autophagy-lysosomal function declines with age in human brain, which in part due to the high oxidative stress. (michaeljfox.org)
  • In addition, we will study the effect of inactivation of autophagy on oxidative stress level, striatal dopamine content and dopamine neuron degeneration. (michaeljfox.org)
  • Bovine mammary epithelial cells after calving undergo serious metabolic challenges and oxidative stress both of which could compromise autophagy. (biomedcentral.com)
  • Tessitore A, Pirozzi M, Auricchio A. Abnormal autophagy, ubiquitination, inflammation and apoptosis are dependent upon lysosomal storage and are useful biomarkers of mucopolysaccharidosis VI. (medlineplus.gov)
  • Also in mice, irinotecan treatment induced hepatic ACOX1 expression, ERK phosphorylation and inflammation, as well as impairment of autophagy and significant steatosis. (bmj.com)
  • Conclusions Irinotecan induces hepatic steatosis via autophagy impairment and inflammation via ERK activation. (bmj.com)
  • Adipocyte autophagy limits gut inflammation by controlling oxylipin and IL-10. (ox.ac.uk)
  • While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. (ox.ac.uk)
  • Studies of microglial gene manipulation in mouse models of Alzheimer's disease (AD) amyloidopathy can cause unpredictable effects on various key endpoints, including amyloidosis, inflammation, neuritic dystrophy, neurodegeneration, and learning behavior. (bvsalud.org)
  • Lyset knockout mice exhibited MLII-like phenotypes and human pathogenic LYSET alleles failed to restore lysosomal sorting defects. (stanford.edu)
  • Number 1 Blocking phosphorylation of STAT3 by NSC74859 induces HNSCC AZD3463 cell death Targeting p-STAT3 by NSC74859 induces autophagy in HNSCC cells Autophagy and apoptosis often simultaneously happen [14 15 Therefore we also examined whether or not NSC74859 induces autophagy in HNSCC cells through morphological and biochemical analyses. (crispr-reagents.com)
  • The function of gene in oncogenesis is certainly unsure still, and dysregulation of gene provides hardly ever been defined in Millimeter, nor various other malignancies, before. (forgetmenotinitiative.org)
  • The expression profiles and clinical information of autophagy gene sets were downloaded from TCGA and GSE52903 queues as training and validation sets. (hindawi.com)
  • After cloning the antibody genes into an expression vector, this is then transfected into an appropriate host cell line for antibody expression. (cellsignal.com)
  • Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. (frontiersin.org)
  • As Postdoc she developed innovative in vivo AAV gene therapy approaches based on liver gene transfer or multi-tissue gene expression to target the multi-organ manifestations of Pompe disease, a LSD that presents with neuromuscular impairment. (stanford.edu)
  • Autophagy was detected using acridine orange staining and real-time PCR for Lc3 and Beclin1 genes expression. (ijpsonline.com)
  • The expression levels of apoptosis-related genes Bcl2 and Bax were determined by real-time PCR. (ijpsonline.com)
  • The expression levels of autophagy-related genes, Lc3 and Beclin1 increased in cells treated with 1.5 mg/ml of Solanum nigrum extract. (ijpsonline.com)
  • RESULTS: KDM6B expression levels in HCC cells correlated with the 5-hydroxymethylcytosine levels in the KDM6B gene body region. (bvsalud.org)
  • An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. (bvsalud.org)
  • We therefore compare behavioral abnormalities, gene expression patterns, lysosomal activity, and TDP‐43 pathology in single and double knockout animals. (synergy-munich.de)
  • Gene expression analysis reveals an upregulation of molecular signature characteristic for disease‐associated microglia and autophagy. (synergy-munich.de)
  • Autophagy and lysosomal related protein expression patterns in human glioblastoma. (ox.ac.uk)
  • PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. (ox.ac.uk)
  • On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. (icr.ac.uk)
  • The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. (icr.ac.uk)
  • Finally, consistent with the differential expression of genes associated with proteasomal degradation in cln5 - cells, we also observed elevated amounts of a proteasome subunit and reduced proteasome 20S activity during cln5 - growth and starvation. (frontiersin.org)
  • The formation of GFP-LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. (nih.gov)
  • Our objectives are to investigate the synergistic effects of GSK-3β in combination with autophagy inhibitors to evade GSK-3β drug resistance. (mdpi.com)
  • GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). (stanford.edu)
  • Mutation of gene is usually associated with Chediak-Higashi syndrome (CHS), a rare autosomal recessive lysosomal disorder with hematological and immunological abnormalities [13]. (forgetmenotinitiative.org)
  • In general, transplantation yields the best results when performed early in the course of the disease (ie, in an asymptomatic affected sibling of a child with a lysosomal storage disorder), in centers with experience in performing transplantations to treat inherited metabolic disorders, and in patients healthy enough to tolerate the conditioning and transplantation regimen. (medscape.com)
  • Gene therapy is experimental but in the future may help correct both somatic and neurologic abnormalities in a lysosomal storage disorder. (medscape.com)
  • We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p, VMA21 is an essential assembly chaperone of the vacuolar ATPase (V-ATPase), the principal mammalian proton pump complex. (nih.gov)
  • Previous work in mammalian models reported altered lysosomal enzyme activity due to mutation or loss of CLN5 . (frontiersin.org)
  • In autophagy, macromolecules in the cytosol are engulfed in a newly formed phagocytic body and subsequently digested in a special lysosome that releases the resultant metabolites back into the cytosol. (invivogen.com)
  • Since the discovery of autophagy-related ( Atg ) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. (nature.com)
  • We also discuss the methods for monitoring autophagy and the roles of drugs, such as chloroquine, verteporfin, and rapamycin, in autophagy. (mendeley.com)
  • Moreover, ATG genes have diverse physiologically important roles in other membrane-trafficking and signaling pathways. (elsevierpure.com)
  • Using a combination of mouse genetics, cell biology and pharmacological approaches my lab has recently demonstrated that autophagy is induced in growth-plate chondrocytes during post-natal development and regulates the secretion of type II collagen (Col2), the major component of cartilage ECM. (ectsoc.org)
  • FGF signalling regulates bone growth through autophagy. (ectsoc.org)
  • In fact, autophagy regulates, and is regulated by, pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), Nod-like receptors (NLRs), RIG-I-like receptors (RLRs), cytosolic DNA sensors (CDS) and Stimulator of Interferon Genes (STING) as well as inflammasomes . (invivogen.com)
  • Moreover, autophagy promotes paclitaxel resistance in cervical cancer cells [ 9 ]. (hindawi.com)
  • Autophagy is one of the three principal mechanisms used by cells to sequester, remove and recycle waste, the others being proteasomal degradation and phagocytosis. (invivogen.com)
  • To isolate and remove specific threats, cells use a selective form of autophagy in which the targeted cargo must first be tagged by ubquitination. (invivogen.com)
  • These findings indicated that Solanum nigrum extract induced cell death in MDA-MB-468 cells by two distinct mechanisms, apoptosis and autophagy, and these findings further suggest a possibility that this extract could be used to treat triple negative breast cancer. (ijpsonline.com)
  • A previous study reported that the extract of the whole plant of SN activated cell death in hepatoma cells through autophagy and apoptosis [ 7 ]. (ijpsonline.com)
  • Autophagy is a lysosomal degradation process that leads to the regeneration of new cells. (mendeley.com)
  • Microarray and chromatin immunoprecipitation analyses using KDM6B-knockout (KO) cells were used to identify KDM6B target genes. (bvsalud.org)
  • Specifically, a decrease of H3K27me3 occupancy at TP53 gene promoter, due to increased KDM6B activity, was observed in radioresistant PCa cells. (bvsalud.org)
  • The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. (icr.ac.uk)
  • Upon nutrient deprivation, autophagy is often up-regulated in response to metabolic stress and excessive organelle damage to facilitate aggregated protein removal and provide energy for cells [ 13 ]. (biomedcentral.com)
  • or gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells ( (forgetmenotinitiative.org)
  • The manifestation of is usually shown to impact lysosomal size, granule size, and autophagy in human cells [12]. (forgetmenotinitiative.org)
  • No.: SR300809, USA) were used to silence the respective gene in RPMI 8226 cells. (forgetmenotinitiative.org)
  • Genes concerned in cell cycle regulation as well as DNA replication had been found to be down regulated in mammospheres, that is in accordance with the lowered development fee that cells exhibit underneath serum no cost suspension condi tions. (pkc-inhibitors.com)
  • The ARSB gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). (medlineplus.gov)
  • These soluble hydrolases are tagged with mannose-6-phosphate (M6P) moieties in sequential reactions by the Golgi-resident GlcNAc-1-phosphotransferase complex and NAGPA/UCE/uncovering enzyme (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), which allows their delivery to endosomal/lysosomal compartments through trafficking mediated by cation-dependent and -independent mannose-6-phosphate receptors (MPRs). (stanford.edu)
  • We renamed TMEM251 to LYSET (lysosomal enzyme trafficking factor) to establish nomenclature reflective to this gene's function. (stanford.edu)
  • The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. (stanford.edu)
  • Here, we used genome-scale CRISPR screens to identify Lysosomal Enzyme Trafficking factor (LYSET) as essential for infection by cathepsin-dependent viruses including SARS-CoV-2. (stanford.edu)
  • In this study, we used comparative transcriptomics to identify differentially expressed genes underlying cln5 -deficiency phenotypes during growth and the early stages of multicellular development. (frontiersin.org)
  • These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. (molcells.org)
  • Autophagy is also one of the most important cytoplasmic recycling mechanisms [ 5 ]. (hindawi.com)
  • Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries. (bvsalud.org)
  • We investigated the molecular mechanism and role of KDM6B downregulation in NAFLD-related HCC after the KDM6B gene was identified using microarray analysis as commonly downregulated in mouse NAFLD-related HCC and human nonhepatitis B and nonhepatitis C viral-HCC. (bvsalud.org)
  • GSEA enrichment analysis showed the main enrichment being in KRAS activation, genes defining epithelial and mesenchymal transition (EMT), raised in response to the low oxygen level (hypoxia) gene and NF- k B in response to TNF. (hindawi.com)
  • In this study, switching off the gene coding for XPO1 (xpo-1) led to improved autophagy and enrichment of the transcription factor HLH-30 in the nucleus. (longlonglife.org)
  • Brown University researchers therefore found that genetically and pharmacologically inhibiting XPO1 significantly increased nuclear enrichment in HLH-30 and improved autophagy, resulting in proteostasis benefits and increased longevity. (longlonglife.org)
  • In this study, we constructed risk signatures of autophagy-related genes (ARGs) to predict the prognosis of cervical cancer. (hindawi.com)
  • However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. (frontiersin.org)
  • Further absolute shrinkage and selection operator (LASSO) and multivariable COX regression yielded an autophagy genetic risk model consisting of eight genes. (hindawi.com)
  • GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (qxmd.com)
  • This in turn reduces lysosomal degradative ability and blocks autophagy. (wikipedia.org)
  • Decreased VMA21 raises lysosomal pH which reduces lysosomal degradative ability and blocks autophagy. (nih.gov)
  • Disintegration of the inner membrane exposes the sequestered cytoplasmic cargo to lysosomal hydrolases, which break down the material into its constituent metabolites 1, 2 . (invivogen.com)
  • Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers. (synergy-munich.de)
  • During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. (frontiersin.org)
  • Through the action of our specific drug candidates to inhibit the ApoE4 protein we will, therefore, restore the lysosomal autophagy necessary for efficient clearance of large aggregates, which, as we reported, is repressed in the brains of those who inherit one or both APOE4 genes. (hhs.gov)
  • It is due to a mutation in VMA21 gene - the human homolog of the yeast Vma21p protein. (wikipedia.org)
  • Besides CHS, mutation in gene is usually one of the important factors that trigger hemophagocytic lymphohistiocytosis, a insufficiency in resistant program function, and life-threatening disease characterized by uncontrolled macrophage and T-cell account activation [14]. (forgetmenotinitiative.org)
  • Pretreatment with the multityrosine kinase inhibitor sorafenib did not affect autophagy impairment and steatosis but significantly reduced ERK phosphorylation and inflammatory response in irinotecan-treated hepatocytes and murine livers. (bmj.com)
  • Thus, a crucial challenge facing researchers is to distinguish "true" autophagy signaling from other types of autophagy-protein signaling. (invivogen.com)
  • Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice. (synergy-munich.de)
  • We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. (bvsalud.org)
  • Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. (bvsalud.org)
  • Alternative splicing of this gene results in multiple transcript variants. (nih.gov)