scholarly journals Astrocytes: Emerging stars in leukodystrophy pathogenesis

2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Angela Lanciotti ◽  
Maria Brignone ◽  
Enrico Bertini ◽  
Tamara Petrucci ◽  
Francesca Aloisi ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Ion Homeostasis ◽  
Primary Role ◽  
Gene Encoding ◽  
Pathophysiological Role ◽  
The Central Nervous System ◽  
Vanishing White Matter Disease ◽  
Almost All ◽  
And Function

AbstractAstrocytes are the predominant glial cell population in the central nervous system (CNS). Once considered only passive scaffolding elements, astrocytes are now recognised as cells playing essential roles in CNS development and function. They control extracellular water and ion homeostasis, provide substrates for energy metabolism, and regulate neurogenesis, myelination and synaptic transmission. Due to these multiple activities astrocytes have been implicated in almost all brain pathologies, contributing to various aspects of disease initiation, progression and resolution. Evidence is emerging that astrocyte dysfunction can be the direct cause of neurodegeneration, as shown in Alexander’s disease where myelin degeneration is caused by mutations in the gene encoding the astrocyte-specific cytoskeleton protein glial fibrillary acidic protein. Recent studies point to a primary role for astrocytes in the pathogenesis of other genetic leukodystrophies such as megalencephalic leukoencephalopathy with subcortical cysts and vanishing white matter disease. The aim of this review is to summarize current knowledge of the pathophysiological role of astrocytes focusing on their contribution to the development of the above mentioned leukodystrophies and on new perspectives for the treatment of neurological disorders.

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

scholarly journals The Role of Astrocytes in the Neurorepair Process

2021 ◽  
Vol 9 ◽  
Author(s):  
Raphaela Almeida Chiareli ◽  
Gustavo Almeida Carvalho ◽  
Bruno Lemes Marques ◽  
Lennia Soares Mota ◽  
Onésia Cristina Oliveira-Lima ◽  
...  
Keyword(s):  
Brain Damage ◽  
Current Knowledge ◽  
Reactive Astrocytes ◽  
Synaptic Activity ◽  
Ionic Homeostasis ◽  
The Central Nervous System ◽  
And Function ◽  
Complex Signaling ◽  
Molecular Bases

Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Thus, reactive astrocytes release several signaling molecules that modulates and contributes to the defense against injuries and infection in the central nervous system. Therefore, deciphering the complex signaling pathways of reactive astrocytes after brain damage can contribute to the neuroinflammation control and reveal new molecular targets to stimulate neurorepair process. In this review, we present the current knowledge about the role of astrocytes in brain damage and repair, highlighting the cellular and molecular bases involved in synaptogenesis and neurogenesis. In addition, we present new approaches to modulate the astrocytic activity and potentiates the neurorepair process after brain damage.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska
Keyword(s):  
Current Knowledge ◽  
Stress Factors ◽  
Oxygenic Photosynthesis ◽  
Ros Generation ◽  
Main Site ◽  
Storage Lipids ◽  
Abiotic Stress Factors ◽  
Cell Components ◽  
And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

scholarly journals Non-Coding RNA in Pancreas and β-Cell Development

2018 ◽  
Vol 4 (4) ◽  
pp. 41 ◽  
Author(s):  
Wilson K. M. Wong ◽  
Anja E. Sørensen ◽  
Mugdha V. Joglekar ◽  
Anand A. Hardikar ◽  
Louise T. Dalgaard
Keyword(s):  
Cell Function ◽  
Islet Cells ◽  
Current Knowledge ◽  
Cell Development ◽  
Pancreas Development ◽  
Β Cell ◽  
Neighboring Gene ◽  
Non Coding Rnas ◽  
And Function

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

scholarly journals T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Kiekens ◽  
Wouter Van Loocke ◽  
Sylvie Taveirne ◽  
Sigrid Wahlen ◽  
Eva Persyn ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Current Knowledge ◽  
Functional Differentiation ◽  
Cell Maturation ◽  
Hematopoietic Stem ◽  
And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

scholarly journals The Urothelium: Life in a Liquid Environment

2020 ◽  
Vol 100 (4) ◽  
pp. 1621-1705 ◽  
Author(s):  
Marianela G. Dalghi ◽  
Nicolas Montalbetti ◽  
Marcelo D. Carattino ◽  
Gerard Apodaca
Keyword(s):  
Current Knowledge ◽  
Nerve Fibers ◽  
Liquid Environment ◽  
Afferent Nerve Fibers ◽  
Proximal Urethra ◽  
Key Aspects ◽  
And Function ◽  
Solute Composition ◽  
Extended Discussion

The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment and communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the past decade. After familiarizing the reader with key aspects of urothelial histology, we describe new insights into urothelial development and regeneration. This is followed by an extended discussion of urothelial barrier function, including information about the roles of the glycocalyx, ion and water transport, tight junctions, and the cellular and tissue shape changes and other adaptations that accompany expansion and contraction of the lower urinary tract. We also explore evidence that the urothelium can alter the water and solute composition of urine during normal physiology and in response to overdistension. We complete the review by providing an overview of our current knowledge about the urothelial environment, discussing the sensor and transducer functions of the urothelium, exploring the role of circadian rhythms in urothelial gene expression, and describing novel research tools that are likely to further advance our understanding of urothelial biology.

scholarly journals MicroRNAs in brain development and cerebrovascular pathophysiology

2019 ◽  
Vol 317 (1) ◽  
pp. C3-C19 ◽  
Author(s):  
Qingyi Ma ◽  
Lubo Zhang ◽  
William J. Pearce
Keyword(s):  
Brain Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Great Promise ◽  
Ischemic Brain ◽  
Neural Lineage ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
And Function

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via base-paring with complementary sequences of the 3′-untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology. We review recent progress of the miRNA-based mechanisms in neuronal and cerebrovascular development as well as their role in hypoxic-ischemic brain injury. These findings hold great promise, not just for deeper understanding of basic brain biology but also for building new therapeutic strategies for prevention and treatment of pathologies such as cerebral ischemia.

scholarly journals Recent advances in our understanding of the structure and function of more unusual cation channels

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 123
Author(s):  
Brandon M. Brown ◽  
Hai M. Nguyen ◽  
Heike Wulff
Keyword(s):  
Cation Channels ◽  
Inner Life ◽  
Sodium Potassium ◽  
Recent Advances ◽  
Pathophysiological Role ◽  
New Type ◽  
Voltage Gated Channels ◽  
Function Relationship ◽  
And Function

As their name implies, cation channels allow the regulated flow of cations such as sodium, potassium, calcium, and magnesium across cellular and intracellular membranes. Cation channels have long been known for their fundamental roles in controlling membrane potential and excitability in neurons and muscle. In this review, we provide an update on the recent advances in our understanding of the structure–function relationship and the physiological and pathophysiological role of cation channels. The most exciting developments in the last two years, in our opinion, have been the insights that cryoelectron microscopy has provided into the inner life and the gating of not only voltage-gated channels but also mechanosensitive and calcium- or sodium-activated channels. The mechanosensitive Piezo channels especially have delighted the field not only with a fascinating new type of structure but with important roles in blood pressure regulation and lung function.

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