scholarly journals The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches

2019 ◽  
Vol 9 ◽  
Author(s):  
Dongwei Xu ◽  
Min Xu ◽  
Seogsong Jeong ◽  
Yihan Qian ◽  
Hailong Wu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches

scholarly journals Targeting of Secretory Proteins as a Therapeutic Strategy for Treatment of Nonalcoholic Steatohepatitis (NASH)

2020 ◽  
Vol 21 (7) ◽  
pp. 2296
Author(s):  
Kyeongjin Kim ◽  
Kook Hwan Kim
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Secretory Protein ◽  
Secretory Proteins ◽  
Therapeutic Approaches ◽  
Nonalcoholic Fatty Liver

Nonalcoholic steatohepatitis (NASH) is defined as a progressive form of nonalcoholic fatty liver disease (NAFLD) and is a common chronic liver disease that causes significant worldwide morbidity and mortality, and has no approved pharmacotherapy. Nevertheless, growing understanding of the molecular mechanisms underlying the development and progression of NASH has suggested multiple potential therapeutic targets and strategies to treat this disease. Here, we review this progress, with emphasis on the functional role of secretory proteins in the development and progression of NASH, in addition to the change of expression of various secretory proteins in mouse NASH models and human NASH subjects. We also highlight secretory protein-based therapeutic approaches that influence obesity-associated insulin resistance, liver steatosis, inflammation, and fibrosis, as well as the gut–liver and adipose–liver axes in the treatment of NASH.

scholarly journals Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 979 ◽  
Author(s):  
Valeria De Pasquale ◽  
Anna Moles ◽  
Luigi Michele Pavone
Keyword(s):  
Molecular Mechanisms ◽  
Protein Processing ◽  
Lysosomal Storage ◽  
Therapeutic Approaches ◽  
Kidney Dysfunction ◽  
Nuclear Membranes ◽  
Intracellular Organelles ◽  
Primary Focus ◽  
Storage Disorders

Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

scholarly journals Emerging role of circadian clock disruption in alcohol-induced liver disease

2018 ◽  
Vol 315 (3) ◽  
pp. G364-G373 ◽  
Author(s):  
Shannon M. Bailey
Keyword(s):  
Liver Disease ◽  
Circadian Clock ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Peripheral Tissues ◽  
New Therapeutic Approaches ◽  
Timing System ◽  
Excessive Alcohol ◽  
The Impact

The detrimental health effects of excessive alcohol consumption are well documented. Alcohol-induced liver disease (ALD) is the leading cause of death from chronic alcohol use. As with many diseases, the etiology of ALD is influenced by how the liver responds to other secondary insults. The molecular circadian clock is an intrinsic cellular timing system that helps organisms adapt and synchronize metabolism to changes in their environment. The clock also influences how tissues respond to toxic, environmental, and metabolic stressors, like alcohol. Consistent with the essential role for clocks in maintaining health, genetic and environmental disruption of the circadian clock contributes to disease. While a large amount of rich literature is available showing that alcohol disrupts circadian-driven behaviors and that circadian clock disruption increases alcohol drinking and preference, very little is known about the role circadian clocks play in alcohol-induced tissue injuries. In this review, recent studies examining the effect alcohol has on the circadian clock in peripheral tissues (liver and intestine) and the impact circadian clock disruption has on development of ALD are presented. This review also highlights some of the rhythmic metabolic processes in the liver that are disrupted by alcohol and potential mechanisms through which alcohol disrupts the liver clock. Improved understanding of the mechanistic links between the circadian clock and alcohol will hopefully lead to the development of new therapeutic approaches for treating ALD and other alcohol-related organ pathologies.

scholarly journals Insight into Salivary Gland Aquaporins

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1547 ◽  
Author(s):  
Claudia D’Agostino ◽  
Osama A. Elkashty ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Simon D. Tran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Role ◽  
Main Role ◽  
Osmotic Gradient ◽  
Therapeutic Approaches ◽  
Potential Therapeutic Target ◽  
Transmembrane Channel ◽  
Saliva Secretion ◽  
Insight Into

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

scholarly journals The Role of Histone Acetylation-/Methylation-Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma

2020 ◽  
Vol 21 (23) ◽  
pp. 8894
Author(s):  
Pradeep Kumar Rajan ◽  
Utibe-Abasi Udoh ◽  
Juan D. Sanabria ◽  
Moumita Banerjee ◽  
Gary Smith ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Modification ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Nuclear Changes ◽  
New Perspective ◽  
Effective Diagnosis

Epigenetics, an inheritable phenomenon, which influences the expression of gene without altering the DNA sequence, offers a new perspective on the pathogenesis of hepatocellular carcinoma (HCC). Nonalcoholic steatohepatitis (NASH) is projected to account for a significant share of HCC incidence due to the growing prevalence of various metabolic disorders. One of the major molecular mechanisms involved in epigenetic regulation, post-translational histone modification seems to coordinate various aspects of NASH which will further progress to HCC. Mounting evidence suggests that the orchestrated events of cellular and nuclear changes during apoptosis can be regulated by histone modifications. This review focuses on the current advances in the study of acetylation-/methylation-mediated histone modification in apoptosis and the implication of these epigenetic regulations in HCC. The reversibility of epigenetic alterations and the agents that can target these alterations offers novel therapeutic approaches and strategies for drug development. Further molecular mechanistic studies are required to enhance information governing these epigenetic modulators, which will facilitate the design of more effective diagnosis and treatment options.

scholarly journals The Role of Androgen Receptor Signaling in Ovarian Cancer

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 176 ◽  
Author(s):  
Taichi Mizushima ◽  
Hiroshi Miyamoto
Keyword(s):  
Ovarian Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Receptor Signaling ◽  
Therapeutic Approaches ◽  
Androgen Receptor Signaling ◽  
Ovarian Carcinogenesis ◽  
Androgen Receptor Activity

Emerging evidence has suggested that androgen receptor signaling plays an important role in ovarian cancer outgrowth. Specifically, androgen receptor activation appears to be associated with increased risks of developing ovarian cancer and inducing tumor progression. However, conflicting findings have also been reported. This review summarizes and discusses the available data indicating the involvement of androgens as well as androgen receptor and related signals in ovarian carcinogenesis and cancer growth. Although the underlying molecular mechanisms for androgen receptor functions in ovarian cancer remain far from being fully understood, current observations may offer effective chemopreventive and therapeutic approaches, via modulation of androgen receptor activity, against ovarian cancer. Indeed, several clinical trials have been conducted to determine the efficacy of androgen deprivation therapy in patients with ovarian cancer.

scholarly journals Nitric Oxide: Exploring the Contextual Link with Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nicholas Asiimwe ◽  
Seung Geun Yeo ◽  
Min-Sik Kim ◽  
Junyang Jung ◽  
Na Young Jeong
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
The Body ◽  
Bioactive Molecules ◽  
Therapeutic Approaches ◽  
Cellular Debris ◽  
And Oxidative Stress ◽  
Proinflammatory Factors

Neuronal inflammation is a systematically organized physiological step often triggered to counteract an invading pathogen or to rid the body of damaged and/or dead cellular debris. At the crux of this inflammatory response is the deployment of nonneuronal cells: microglia, astrocytes, and blood-derived macrophages. Glial cells secrete a host of bioactive molecules, which include proinflammatory factors and nitric oxide (NO). From immunomodulation to neuromodulation, NO is a renowned modulator of vast physiological systems. It essentially mediates these physiological effects by interacting with cyclic GMP (cGMP) leading to the regulation of intracellular calcium ions. NO regulates the release of proinflammatory molecules, interacts with ROS leading to the formation of reactive nitrogen species (RNS), and targets vital organelles such as mitochondria, ultimately causing cellular death, a hallmark of many neurodegenerative diseases. AD is an enervating neurodegenerative disorder with an obscure etiology. Because of accumulating experimental data continually highlighting the role of NO in neuroinflammation and AD progression, we explore the most recent data to highlight in detail newly investigated molecular mechanisms in which NO becomes relevant in neuronal inflammation and oxidative stress-associated neurodegeneration in the CNS as well as lay down up-to-date knowledge regarding therapeutic approaches targeting NO.

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