scholarly journals The role of whey acidic protein four-disulfide-core proteins in respiratory health and disease

2017 ◽  
Vol 398 (4) ◽  
pp. 425-440 ◽  
Author(s):  
Donna M. Small ◽  
Declan F. Doherty ◽  
Caoifa M. Dougan ◽  
Sinéad Weldon ◽  
Clifford C. Taggart
Keyword(s):  
Protein Function ◽  
Respiratory Health ◽  
Whey Acidic Protein ◽  
Acidic Protein ◽  
Current Evidence ◽  
Core Proteins ◽  
Health And Disease ◽  
Low Molecular Weight Proteins ◽  
Potential Therapeutics

Abstract Members of the whey acidic protein (WAP) or WAP four-disulfide-core (WFDC) family of proteins are a relatively under-explored family of low molecular weight proteins. The two most prominent WFDC proteins, secretory leukocyte protease inhibitor (SLPI) and elafin (or the precursor, trappin-2), have been shown to possess multiple functions including anti-protease, anti-bacterial, anti-viral and anti-inflammatory properties. It is therefore of no surprise that both SLPI and elafin/trappin-2 have been developed as potential therapeutics. Given the abundance of SLPI and elafin/trappin-2 in the human lung, most work in the area of WFDC research has focused on the role of WFDC proteins in protecting the lung from proteolytic attack. In this review, we will outline the current evidence regarding the expanding role of WFDC protein function with a focus on WFDC activity in lung disease as well as emerging data regarding the function of some of the more recently described WFDC proteins.

scholarly journals Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

2020 ◽  
Vol 21 (5) ◽  
pp. 1798 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Edzard Schwedhelm ◽  
Hans Worthmann ◽  
Chi-un Choe
Keyword(s):  
Ischemic Stroke ◽  
Vascular Function ◽  
Cerebrovascular Diseases ◽  
Current Evidence ◽  
Clinical Implications ◽  
Pathophysiological Role ◽  
Health And Disease ◽  
Oxide Synthase ◽  
Derivatives Of

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

scholarly journals Evolving Concepts of Glycogen-Selective Autophagy

2021 ◽  
Author(s):  
Parisa Koutsifeli ◽  
Upasna Varma ◽  
Lorna Daniels ◽  
Marco Annandale ◽  
Xun Li ◽  
...  
Keyword(s):  
Degradation Pathway ◽  
Specific Protein ◽  
Current Evidence ◽  
Evolutionary Stage ◽  
Major Pathway ◽  
Selective Autophagy ◽  
Protein Partners ◽  
Health And Disease ◽  
Autophagy Pathway

Macro-autophagy is an essential cellular process involved in degradation of aberrant organelles and proteins. Initially proposed to be a ‘bulk’ degradation pathway, a more nuanced appreciation of selective autophagy pathways has emerged in recent years. The discovery of a glycogen-selective autophagy pathway (‘glycophagy’) has highlighted the importance of autophagy in regulating cellular metabolic homeostasis and identified a novel non-canonical major pathway of glycogen flux. The field of glycogen autophagy research is at an early evolutionary stage, but already it is clear that the implications of these discoveries are far-reaching and provide scope for multi-disciplinary investigations into the role of glycophagy in health and disease. With potential cognate protein partners identified, the opportunities for targeted intervention have become viable. Here we review the current evidence relating to specific protein mediators involved in glycophagy, and highlight areas of uncertainty that provide opportunity for further investigation.

Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids

2015 ◽  
Vol 46 (1) ◽  
pp. 27-45 ◽  
Author(s):  
E. Appiah-Kusi ◽  
E. Leyden ◽  
S. Parmar ◽  
V. Mondelli ◽  
P. McGuire ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Psychotic Disorders ◽  
Endocannabinoid System ◽  
Current Evidence ◽  
Response To Stress ◽  
Health And Disease ◽  
Stress Response System ◽  
Precise Role

The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.

Regulatory role of NGFs in neurocognitive functions

2017 ◽  
Vol 28 (6) ◽  
pp. 649-673 ◽  
Author(s):  
Ashutosh Kumar ◽  
Vikas Pareek ◽  
Muneeb A. Faiq ◽  
Pavan Kumar ◽  
Khursheed Raza ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Current Evidence ◽  
Future Research ◽  
Neurocognitive Dysfunction ◽  
Neurocognitive Functions ◽  
The Central Nervous System ◽  
Health And Disease

AbstractNerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain. They have also been associated extensively with brain disorders characterized by neurocognitive dysfunction. In the present article, we aimed to make an exhaustive review of literature to get a comprehensive view on the role of NGFs in neurocognitive functions in health and disease. Starting with historical perspective, distribution in adult brain, implied molecular mechanisms, and developmental basis, this article further provides a detailed account of NGFs’ role in specified neurocognitive functions. Furthermore, it discusses plausible NGF-based homeostatic and adaptation mechanisms operating in the pathogenesis of neurocognitive disorders and has presents a survey of such disorders. Finally, it elaborates on current evidence and future possibilities in therapeutic applications of NGFs with an emphasis on recent research updates in drug delivery mechanisms. Conclusive remarks of the article make a strong case for plausible role of NGFs in comprehensive regulation of the neurocognitive functions and pathogenesis of related disorders and advocate that future research should be directed to explore use of NGF-based mechanisms in the prevention of implicated diseases as well as to target these molecules pharmacologically.

scholarly journals Intestinal Barrier Function in Health and Disease—Any Role of SARS-CoV-2?

2020 ◽  
Vol 8 (11) ◽  
pp. 1744
Author(s):  
Lakshya Sharma ◽  
Antonio Riva
Keyword(s):  
Intestinal Barrier ◽  
Therapeutic Strategies ◽  
Structure And Function ◽  
Intestinal Barrier Function ◽  
Current Evidence ◽  
Barrier Functions ◽  
Microbial Dysbiosis ◽  
Health And Disease ◽  
And Function

Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.

scholarly journals A New Type of COP: The Role of Circulating Osteoprogenitor (COP) Cells in Health and Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 44-45
Author(s):  
Gustavo Duque
Keyword(s):  
Aging Process ◽  
Musculoskeletal Diseases ◽  
Current Evidence ◽  
Future Research ◽  
Clinical Utilization ◽  
Therapeutic Uses ◽  
Health And Disease ◽  
New Type

Abstract Circulating osteogenic progenitor (COP) cells are a population of cells in the peripheral blood with the capacity for bone formation and broader differentiation into mesoderm-like cells in vitro. While some of their biological characteristics are documented in vitro, their role in the aging process and the pathogenesis of musculoskeletal diseases remains yet to be thoroughly evaluated. This translational session will go from bench to bedside, reviewing the current evidence on COP cells. In this session, we will provide an overview of the role of COP cells in the aging process and a number of physiological and pathological conditions and identify areas for future research. In addition, we will suggest possible areas for clinical utilization in the management of musculoskeletal diseases, which include novel diagnostic and therapeutic uses.

scholarly journals 683 The role of the WFDC [WAP (Whey acidic protein) four-disulfide core] family members in the epidermis

2018 ◽  
Vol 138 (5) ◽  
pp. S116
Author(s):  
P. Kalinina ◽  
M. Buchberger ◽  
B. Lengauer ◽  
B. Golabi ◽  
L. Beer ◽  
...  
Keyword(s):  
Family Members ◽  
Whey Acidic Protein ◽  
Acidic Protein

scholarly journals Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?

2019 ◽  
Vol 20 (22) ◽  
pp. 5794 ◽  
Author(s):  
Rebeca Piatniczka Iglesia ◽  
Camila Felix de Lima Fernandes ◽  
Bárbara Paranhos Coelho ◽  
Mariana Brandão Prado ◽  
Maria Isabel Melo Escobar ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Types ◽  
Current Evidence ◽  
Health And Disease ◽  
Shock Proteins ◽  
Mitochondrial Chaperones ◽  
Different Cell Types ◽  
Small Subpopulation

Heat shock proteins (HSPs) are evolutionary conserved proteins that work as molecular chaperones and perform broad and crucial roles in proteostasis, an important process to preserve the integrity of proteins in different cell types, in health and disease. Their function in cancer is an important aspect to be considered for a better understanding of disease development and progression. Glioblastoma (GBM) is the most frequent and lethal brain cancer, with no effective therapies. In recent years, HSPs have been considered as possible targets for GBM therapy due their importance in different mechanisms that govern GBM malignance. In this review, we address current evidence on the role of several HSPs in the biology of GBMs, and how these molecules have been considered in different treatments in the context of this disease, including their activities in glioblastoma stem-like cells (GSCs), a small subpopulation able to drive GBM growth. Additionally, we highlight recent works that approach other classes of chaperones, such as histone and mitochondrial chaperones, as important molecules for GBM aggressiveness. Herein, we provide new insights into how HSPs and their partners play pivotal roles in GBM biology and may open new therapeutic avenues for GBM based on proteostasis machinery.

scholarly journals Mouse whey acidic protein is a novel member of the family of ‘four-disulfide core’ proteins

1982 ◽  
Vol 10 (8) ◽  
pp. 2677-2684 ◽  
Author(s):  
Lothar G. Hennighausen ◽  
Albrecht E. Sippel
Keyword(s):  
Whey Acidic Protein ◽  
Acidic Protein ◽  
Core Proteins ◽  
The Family

Role of the Adventitia in Pulmonary Vascular Remodeling

Physiology ◽  
2006 ◽  
Vol 21 (2) ◽  
pp. 134-145 ◽  
Author(s):  
Kurt R. Stenmark ◽  
Neil Davie ◽  
Maria Frid ◽  
Evgenia Gerasimovskaya ◽  
Mita Das
Keyword(s):  
Vascular Function ◽  
Vessel Wall ◽  
Vascular Wall ◽  
Current Evidence ◽  
Wall Function ◽  
Response To Stress ◽  
Health And Disease ◽  
Adventitial Fibroblast ◽  
Structural Behaviors

An increasing volume of experimental data indicates that the adventitial fibroblast, in both the pulmonary and systemic circulations, is a critical regulator of vascular wall function in health and disease. A rapidly emerging concept is that the vascular adventitia acts as biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. In response to stress or injury, resident adventitial cells can be activated and reprogrammed to exhibit different functional and structural behaviors. In fact, under certain conditions, the adventitial compartment may be considered the principal injury-sensing tissue of the vessel wall. In response to vascular stresses such as overdistension and hypoxia, the adventitial fibroblast is activated and undergoes phenotypic changes, which include proliferation, differentiation, upregulation of contractile and extracellular matrix proteins, and release of factors that directly affect medial smooth muscle cell tone and growth and that stimulate recruitment of inflammatory and progenitor cells to the vessel wall. Each of these changes in fibroblast phenotype modulates either directly or indirectly changes in overall vascular function and structure. The purpose of this review is to present the current evidence demonstrating that the adventitial fibroblast acts as a key regulator of pulmonary vascular function and structure from the “outside-in.”

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