scholarly journals Presynaptic AMPA Receptors in Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2260
Author(s):  
Letizia Zanetti ◽  
Maria Regoni ◽  
Elena Ratti ◽  
Flavia Valtorta ◽  
Jenny Sassone
Keyword(s):  
Ampa Receptors ◽  
Plasma Membranes ◽  
Actin Dynamics ◽  
Axonal Pathology ◽  
Pathological Conditions ◽  
Pain Transmission ◽  
Pharmacological Targets ◽  
Health And Disease ◽  
Excitatory Neurotransmission

AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.

scholarly journals Polyphenols as Modulators of Aquaporin Family in Health and Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Diana Fiorentini ◽  
Laura Zambonin ◽  
Francesco Vieceli Dalla Sega ◽  
Silvana Hrelia
Keyword(s):  
Plasma Membranes ◽  
Skin Diseases ◽  
Water Channel ◽  
Bioactive Molecules ◽  
Food Sources ◽  
Major Function ◽  
Cell Plasma ◽  
Original Analysis ◽  
Health And Disease

Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP) isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

Role of cardiolipin alterations in mitochondrial dysfunction and disease

2007 ◽  
Vol 292 (1) ◽  
pp. C33-C44 ◽  
Author(s):  
Adam J. Chicco ◽  
Genevieve C. Sparagna
Keyword(s):  
Mitochondrial Dysfunction ◽  
Acyl Chain ◽  
Causative Factor ◽  
Biological Tissues ◽  
Barth Syndrome ◽  
Inner Mitochondrial Membrane ◽  
Pathological Conditions ◽  
Chain Composition ◽  
Health And Disease

Cardiolipin (CL) is a structurally unique dimeric phospholipid localized in the inner mitochondrial membrane where it is required for optimal mitochondrial function. In addition to its role in maintaining membrane potential and architecture, CL is known to provide essential structural and functional support to several proteins involved in mitochondrial bioenergetics. A loss of CL content, alterations in its acyl chain composition, and/or CL peroxidation have been associated with mitochondrial dysfunction in multiple tissues in a variety of pathological conditions, including ischemia, hypothyroidism, aging, and heart failure. Recently, aberrations in CL metabolism have been implicated as a primary causative factor in the cardioskeletal myopathy known as Barth syndrome, underscoring an important role of CL in human health and disease. The purpose of this review is to provide an overview of evidence that has linked changes in the CL profile to mitochondrial dysfunction in various pathological conditions. In addition, a brief overview of CL function and biosynthesis, and a discussion of methods used to examine CL in biological tissues are provided.

scholarly journals Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease

2019 ◽  
Vol 20 (15) ◽  
pp. 3673 ◽  
Author(s):  
Lismont ◽  
Revenco ◽  
Fransen
Keyword(s):  
Hydrogen Peroxide ◽  
Molecular Mechanisms ◽  
Signaling Network ◽  
H2o2 Production ◽  
Peroxisomal Enzyme ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Precise Role ◽  
Insight Into

Hydrogen peroxide (H2O2), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H2O2 metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.

scholarly journals The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1679 ◽  
Author(s):  
Tulasi Yadati ◽  
Tom Houben ◽  
Albert Bitorina ◽  
Ronit Shiri-Sverdlov
Keyword(s):  
Vital Role ◽  
Intracellular Protein ◽  
Pathological Conditions ◽  
Wide Range ◽  
Intracellular Protein Degradation ◽  
Health And Disease ◽  
Lysosomal Proteases ◽  
Shed Light ◽  
Physiological Substrates

Cathepsins are the most abundant lysosomal proteases that are mainly found in acidicendo/lysosomal compartments where they play a vital role in intracellular protein degradation,energy metabolism, and immune responses among a host of other functions. The discovery thatcathepsins are secreted and remain functionally active outside of the lysosome has caused a paradigmshift. Contemporary research has unraveled many versatile functions of cathepsins in extralysosomallocations including cytosol and extracellular space. Nevertheless, extracellular cathepsins are majorlyupregulated in pathological states and are implicated in a wide range of diseases including cancerand cardiovascular diseases. Taking advantage of the dierential expression of the cathepsinsduring pathological conditions, much research is focused on using cathepsins as diagnostic markersand therapeutic targets. A tailored therapeutic approach using selective cathepsin inhibitors isconstantly emerging to be safe and ecient. Moreover, recent development of proteomic-basedapproaches for the identification of novel physiological substrates oers a major opportunity tounderstand the mechanism of cathepsin action. In this review, we summarize the available evidenceregarding the role of cathepsins in health and disease, discuss their potential as biomarkers ofdisease progression, and shed light on the potential of extracellular cathepsin inhibitors as safetherapeutic tools.

scholarly journals Role of mTOR in Glucose and Lipid Metabolism

2018 ◽  
Vol 19 (7) ◽  
pp. 2043 ◽  
Author(s):  
Zhuo Mao ◽  
Weizhen Zhang
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factors ◽  
Lipid Metabolism ◽  
Mammalian Target Of Rapamycin ◽  
Adipose Tissues ◽  
Glucose And Lipid Metabolism ◽  
Pathological Conditions ◽  
Pharmacological Targets

The mammalian target of rapamycin, mTOR is the master regulator of a cell’s growth and metabolic state in response to nutrients, growth factors and many extracellular cues. Its dysregulation leads to a number of metabolic pathological conditions, including obesity and type 2 diabetes. Here, we review recent findings on the role of mTOR in major metabolic organs, such as adipose tissues, liver, muscle, pancreas and brain. And their potentials as the mTOR related pharmacological targets will be also discussed.

scholarly journals Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 90 ◽  
Author(s):  
Simone Mader ◽  
Lior Brimberg
Keyword(s):  
Water Channel ◽  
Aquaporin 4 ◽  
Target Antigen ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Inflammatory Autoimmune Disease ◽  
The Brain ◽  
Astrocytic Endfeet

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer’s disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.

scholarly journals The Teleost Thymus in Health and Disease: New Insights from Transcriptomic and Histopathological Analyses of Turbot, Scophthalmus maximus

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 221
Author(s):  
Paolo Ronza ◽  
Diego Robledo ◽  
Ana Paula Losada ◽  
Roberto Bermúdez ◽  
Belén G. Pardo ◽  
...  
Keyword(s):  
Adaptive Immune System ◽  
Scophthalmus Maximus ◽  
Infected Fish ◽  
Lymphoid Organ ◽  
Thymic Function ◽  
Pathological Conditions ◽  
Myxozoan Parasite ◽  
Health And Disease ◽  
Turbot Scophthalmus Maximus

The thymus is a primary lymphoid organ that plays a pivotal role in the adaptive immune system. The immunobiology of the thymus in fish is considered to be similar to that of mammals, but it is actually poorly characterized in several cultured teleost species. In particular, while investigations in human and veterinary medicine have highlighted that the thymus can be affected by different pathological conditions, little is known about its response during disease in fish. To better understand the role of the thymus under physiological and pathological conditions, we conducted a study in turbot (Scophthalmus maximus), a commercially valuable flatfish species, combining transcriptomic and histopathological analyses. The myxozoan parasite Enteromyxum scophthalmi, which represents a major challenge to turbot production, was used as a model of infection. The thymus tissues of healthy fish showed overrepresented functions related to its immunological role in T-cell development and maturation. Large differences were observed between the transcriptomes of control and severely infected fish. Evidence of inflammatory response, apoptosis modulation, and declined thymic function associated with loss of cellularity was revealed by both genomic and morphopathological analyses. This study presents the first description of the turbot thymus transcriptome and provides novel insights into the role of this organ in teleosts’ immune responses.

Heme Oxygenase and the Skin in Health and Disease

2018 ◽  
Vol 24 (20) ◽  
pp. 2303-2310 ◽  
Author(s):  
Imre Lorinc Szabo ◽  
Anna Kenyeres ◽  
Andrea Szegedi ◽  
Attila Gabor Szollosi
Keyword(s):  
Heme Oxygenase ◽  
Skin Diseases ◽  
Recent Decade ◽  
Cellular Damage ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Malignant Skin ◽  
Health And Disease ◽  
A Site

The skin is often introduced as the largest organ of the human body which – being uniquely exposed to external stress – faces several types of challenges, from physical, chemical, biological, and immunological origin. Therefore, the skin is also a site where inflammation, oxidative stress and cellular damage occurs regularly. Heme oxygenase (HO), primarily functioning in the catabolism of heme, is a very important cytoprotective enzyme that has antioxidant, anti-inflammatory and anti-apoptotic properties. Given the need for an enzyme with such a combination of attributes in the skin, it is not surprising that HO is involved in physiological processes as well as pathological conditions of the skin. In the recent decade, a huge effort was undertaken to identify treatments that modify HO-activity for the treatment of inflammatory or malignant skin diseases. In this review, we highlight the role of HO in the skin in physiological conditions as well as in relevant dermatological diseases such as atopic dermatitis, psoriasis and melanoma.

Effects of neuronal drebrin on actin dynamics

2021 ◽  
Author(s):  
Elena E. Grintsevich
Keyword(s):  
Synaptic Plasticity ◽  
Posttranslational Modifications ◽  
Neurodegenerative Disorders ◽  
Neuronal Migration ◽  
Recent Progress ◽  
Actin Dynamics ◽  
Cytoskeletal Dynamics ◽  
Health And Disease ◽  
Made In

Drebrin is a key regulator of actin cytoskeleton in neuronal cells which is critical for synaptic plasticity, neuritogenesis, and neuronal migration. It is also known to orchestrate a cross-talk between actin and microtubules. Decreased level of drebrin is a hallmark of multiple neurodegenerative disorders such as Alzheimer's disease. Despite its established importance in health and disease, we still have a lot to learn about drebrin's interactome and its effects on cytoskeletal dynamics. This review aims to summarize the recently reported novel effects of drebrin on actin and its regulators. Here I will also reflect on the most recent progress made in understanding of the role of drebrin isoforms and posttranslational modifications on its functionality.

scholarly journals Challenges in Exosome Isolation and Analysis in Health and Disease

2019 ◽  
Vol 20 (19) ◽  
pp. 4684 ◽  
Author(s):  
Nils Ludwig ◽  
Theresa L. Whiteside ◽  
Torsten E. Reichert
Keyword(s):  
Overall Survival ◽  
Response To Therapy ◽  
Disease Biomarkers ◽  
Isolation And Characterization ◽  
Pathological Conditions ◽  
Growing Body ◽  
Health And Disease ◽  
Novel Approaches ◽  
Virus Size

A growing body of evidence emphasizes the important role exosomes in different physiological and pathological conditions. Exosomes, virus-size extracellular vesicles (EVs), carry a complex molecular cargo, which is actively processed in the endocytic compartment of parental cells. Exosomes carry and deliver this cargo to recipient cells, serving as an intercellular communication system. The methods for recovery of exosomes from supernatants of cell lines or body fluids are not uniformly established. Yet, studies of the quality and quantity of exosome cargos underlie the concept of “liquid biopsy.” Exosomes are emerging as a potentially useful diagnostic tool and a predictor of disease progression, response to therapy and overall survival. Although many novel approaches to exosome isolation and analysis of their cargos have been introduced, the role of exosomes as diagnostic or prognostic biomarkers of disease remains unconfirmed. This review considers existing challenges to exosome validation as disease biomarkers. Focusing on advantages and limitations of methods for exosome isolation and characterization, approaches are proposed to facilitate further progress in the development of exosomes as biomarkers in human disease.

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