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Clinical Science (London, England :... Nov 2016Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors,... (Review)
Review
Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the 'START' (steroidogenic acute regulatory protein-related lipid transfer) and 'ORP' (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease.
Topics: Animals; Biological Transport; Cholesterol; Disease; Humans; Lipid Metabolism; Phosphoproteins; Receptors, Steroid
PubMed: 27660308
DOI: 10.1042/CS20160339 -
Biochimica Et Biophysica Acta Feb 2015The interferon-regulatory factor (IRF) family comprises nine members in mammals. Although this transcription factor family was originally thought to function primarily... (Review)
Review
The interferon-regulatory factor (IRF) family comprises nine members in mammals. Although this transcription factor family was originally thought to function primarily in the immune system, contributing to both the innate immune response and the development of immune cells, recent advances have revealed that IRFs plays critical roles in other biological processes, such as metabolism. Accordingly, abnormalities in the expression and/or function of IRFs have increasingly been linked to disease. Herein, we provide an update on the recent progress regarding the regulation of immune responses and immune cell development associated with IRFs. Additionally, we discuss the relationships between IRFs and immunity, metabolism, and disease, with a particular focus on the role of IRFs as stress sensors. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
Topics: Animals; Disease; Humans; Immunity; Immunity, Innate; Interferon Regulatory Factors; Metabolism; Models, Biological
PubMed: 24807060
DOI: 10.1016/j.bbadis.2014.04.030 -
Dental Clinics of North America Oct 1986
Review
Topics: Chronic Disease; Disease; Humans; Stress, Physiological
PubMed: 3536627
DOI: No ID Found -
Pharmacological Reviews 2013Autophagy, a process of self-digestion of the cytoplasm and organelles through which cellular components are recycled for reuse or energy production, is an... (Review)
Review
Autophagy, a process of self-digestion of the cytoplasm and organelles through which cellular components are recycled for reuse or energy production, is an evolutionarily conserved response to metabolic stress found in eukaryotes from yeast to mammals. It is noteworthy that autophagy is also associated with various pathophysiologic conditions in which this cellular process plays either a cytoprotective or cytopathic role in response to a variety of stresses such as metabolic, inflammatory, neurodegenerative, and therapeutic stress. It is now generally believed that modulating the activity of autophagy through targeting specific regulatory molecules in the autophagy machinery may impact disease processes, thus autophagy may represent a new pharmacologic target for drug development and therapeutic intervention of various human disorders. Induction or inhibition of autophagy using small molecule compounds has shown promise in the treatment of diseases such as cancer. Depending on context, induction or suppression of autophagy may exert therapeutic effects via promoting either cell survival or death, two major events targeted by therapies for various disorders. A better understanding of the biology of autophagy and the pharmacology of autophagy modulators has the potential for facilitating the development of autophagy-based therapeutic interventions for several human diseases.
Topics: Animals; Autophagy; Disease; Drug Therapy; Humans
PubMed: 23943849
DOI: 10.1124/pr.112.007120 -
Genes & Development Jul 2017Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress.... (Review)
Review
Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress. Eukaryotic cells evolved a set of intracellular signaling pathways, collectively termed the unfolded protein response (UPR), to maintain a productive ER protein-folding environment through reprogramming gene transcription and mRNA translation. The UPR is largely dependent on transcription factors (TFs) that modulate expression of genes involved in many physiological and pathological conditions, including development, metabolism, inflammation, neurodegenerative diseases, and cancer. Here we summarize the current knowledge about these mechanisms, their impact on physiological/pathological processes, and potential therapeutic applications.
Topics: Disease; Endoplasmic Reticulum Stress; Humans; Protein Biosynthesis; Transcription Factors; Transcriptional Activation; Unfolded Protein Response
PubMed: 28860159
DOI: 10.1101/gad.297374.117 -
Cellular and Molecular Life Sciences :... Dec 2021Inflammation is vital to protect the host against foreign organism invasion and cellular damage. It requires tight and concise gene expression for regulation of pro- and... (Review)
Review
Inflammation is vital to protect the host against foreign organism invasion and cellular damage. It requires tight and concise gene expression for regulation of pro- and anti-inflammatory gene expression in immune cells. Dysregulated immune responses caused by gene mutations and errors in post-transcriptional regulation can lead to chronic inflammatory diseases and cancer. The mechanisms underlying post-transcriptional gene expression regulation include mRNA splicing, mRNA export, mRNA localisation, mRNA stability, RNA/protein interaction, and post-translational events such as protein stability and modification. The majority of studies to date have focused on transcriptional control pathways. However, post-transcriptional regulation of mRNA in eukaryotes is equally important and related information is lacking. In this review, we will focus on the mechanisms involved in the pre-mRNA splicing events, mRNA surveillance, RNA degradation pathways, disorders or symptoms caused by mutations or errors in post-transcriptional regulation during innate immunity especially toll-like receptor mediated pathways.
Topics: Animals; Disease; Humans; Immunity; Inflammation; Nonsense Mediated mRNA Decay; Pathogen-Associated Molecular Pattern Molecules; RNA
PubMed: 34971439
DOI: 10.1007/s00018-021-04073-5 -
International Journal of Biological... 2013Autophagy has attracted a lot of attention in recent years. More and more proteins and signaling pathways have been discovered that somehow feed into the autophagy... (Review)
Review
Autophagy has attracted a lot of attention in recent years. More and more proteins and signaling pathways have been discovered that somehow feed into the autophagy regulatory pathways. Regulation of autophagy is complex and condition-specific, and in several diseases, autophagic fluxes are changed. Here, we review the most well-established concepts in this field as well as the reported signaling pathways or components which steer the autophagy machinery. Furthermore, we will highlight how autophagic fluxes are changed in various diseases either as cause for or as response to deal with an altered cellular homeostasis and how modulation of autophagy might be used as potential therapy for such diseases.
Topics: Autophagy; Disease; Humans; Signal Transduction
PubMed: 24339733
DOI: 10.7150/ijbs.6666 -
Annual Review of Cell and Developmental... Oct 2017Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast... (Review)
Review
Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast majority of cellular and organismal functions. To maintain a healthy proteome, cells rely on a network of factors and pathways collectively known as protein quality control (PQC) systems, which not only ensure that newly synthesized proteins reach a functional conformation but also are essential for surveillance, prevention, and rescue of protein defects. The main players of PQC systems are chaperones and protein degradation systems: the ubiquitin-proteasome system and autophagy. Here we provide an integrated overview of the diverse PQC systems in eukaryotic cells in health and diseases, with an emphasis on the key regulatory aspects and their cross talks. We also highlight how PQC regulation may be exploited for potential therapeutic benefit.
Topics: Amino Acids; Animals; Disease; Eukaryotic Cells; Homeostasis; Humans; Proteins; Stress, Physiological
PubMed: 28992440
DOI: 10.1146/annurev-cellbio-111315-125334 -
Nature Reviews. Genetics Dec 2008Sexual dimorphism in anatomical, physiological and behavioural traits are characteristics of many vertebrate species. In humans, sexual dimorphism is also observed in... (Review)
Review
Sexual dimorphism in anatomical, physiological and behavioural traits are characteristics of many vertebrate species. In humans, sexual dimorphism is also observed in the prevalence, course and severity of many common diseases, including cardiovascular diseases, autoimmune diseases and asthma. Although sex differences in the endocrine and immune systems probably contribute to these observations, recent studies suggest that sex-specific genetic architecture also influences human phenotypes, including reproductive, physiological and disease traits. It is likely that an underlying mechanism is differential gene regulation in males and females, particularly in sex steroid-responsive genes. Genetic studies that ignore sex-specific effects in their design and interpretation could fail to identify a significant proportion of the genes that contribute to risk for complex diseases.
Topics: Animals; Asthma; Autoimmune Diseases; Cardiovascular Diseases; Disease; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Genotype; Humans; Male; Quantitative Trait Loci; Sex Characteristics
PubMed: 19002143
DOI: 10.1038/nrg2415 -
Health Psychology Review Dec 2019Research on the Commonsense Self-Regulation Model has emphasised reflective/conscious perceptual processes regarding illness threat (beliefs about symptoms,... (Review)
Review
Research on the Commonsense Self-Regulation Model has emphasised reflective/conscious perceptual processes regarding illness threat (beliefs about symptoms, consequences, timeline, and curability) in predicting and changing coping behaviours. Understanding of illness self-regulation and avenues for intervention might be enriched by consideration of automatic processes that influence the recognition and identification of illness, response to illness, and ongoing management. This article adopts an integrative approach to (1) outline the theoretical importance of implicit processes in patients' self-regulation of illness and methods to study them; (2) review research evidence for these processes, including interventions tested to modify them; and (3) outline avenues for future research. A substantial body of research on implicit processes (cognitive bias and interpretational bias) in illness maintenance in chronic illness has recently been extended to detection and interpretation of acute illness and new perspectives relating to the self-system. There is encouraging evidence that cognitive accessibility of coping and implicit attitudes may impact upon coping behaviours. Procedures that strategically automatise coping responses and create habits have considerable promise. We outline an agenda for future research in which health psychology accepts the challenge posed by the interplay of the reflective and associative systems in promoting effective self-regulation of illness.
Topics: Adaptation, Psychological; Attention; Behavioral Medicine; Chronic Disease; Cognition; Cues; Diagnostic Self Evaluation; Disease; Humans; Models, Psychological; Self-Control
PubMed: 30033853
DOI: 10.1080/17437199.2018.1503559