scholarly journals Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

2020 ◽  
Vol 17 (4) ◽  
pp. 1269 ◽  
Author(s):  
Jan Aaseth ◽  
Aleksandra Buha ◽  
David R. Wallace ◽  
Geir Bjørklund
Keyword(s):  
Central Nervous System ◽  
Trace Metals ◽  
Clinical Phenotype ◽  
Therapeutic Strategies ◽  
Tau Proteins ◽  
Hyperphosphorylated Tau ◽  
Disease Group ◽  
Pathogenic Factors ◽  
The Central Nervous System ◽  
Further Development

Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.

Experiments on Neuromery in Ambystoma punctatum Embryos

Development ◽  
1956 ◽  
Vol 4 (1) ◽  
pp. 66-72
Author(s):  
Bengt Källén
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mitotic Activity ◽  
Present Author ◽  
Similar Nature ◽  
High Mitotic Activity ◽  
The Central Nervous System ◽  
Further Development ◽  
The Brain ◽  
Low Activity

In a series of papers the present author has discussed the nature and significance of the transverse bulges of the central nervous system of vertebrates, long since known as neuromeres. Their formation and further development have been described and it has been shown that they are signs of a proliferation pattern, made up of transverse bands of high mitotic activity alternating with bands of low activity. It has also been demonstrated that the neuromeric pattern is preceded by another pattern of a similar nature, mirrored in the formation of the so-called proneuromeres, and is followed by a third pattern, giving rise to the postneuromeres or transverse bands of migration areas. For further details of these investigations, the reader is referred to Bergquist & Källén (1954). An unsolved question is the nature of the factors that cause the patterning of the mitoses and therefore also the bulging of the brain wall to form neuromeres.

scholarly journals Microglia Mediated Neuroinflammation: Focus on PI3K Modulation

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 137 ◽  
Author(s):  
Antonia Cianciulli ◽  
Chiara Porro ◽  
Rosa Calvello ◽  
Teresa Trotta ◽  
Dario Domenico Lofrumento ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Tissue Damage ◽  
Therapeutic Strategies ◽  
Focused Attention ◽  
Pathogen Invasion ◽  
Wide Range ◽  
Inflammatory Processes ◽  
The Central Nervous System

Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.

scholarly journals Exploring neurodegeneration at the atomic level

2018 ◽  
Vol 40 (5) ◽  
pp. 9-11
Author(s):  
Adam Tozer
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Atomic Level ◽  
Tau Proteins ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Central Nervous System ◽  
The Brain ◽  
Cell Maintenance

Tau proteins are microtubule-associated proteins essential for the correct functioning of neurons. This small family of proteins, 352–441 amino acids in length, are abundant in the brain and exist to stabilize microtubules in neurons and glia (non-neuronal cells of the central nervous system) to ensure correct trafficking of cellular cargo and cell maintenance.

scholarly journals Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiuqi Chen ◽  
Wenmei Lu ◽  
Danhong Wu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rapid Growth ◽  
Nicotinamide Adenine Dinucleotide ◽  
Neurological Disorders ◽  
Potential Role ◽  
Therapeutic Strategies ◽  
Nicotinamide Adenine ◽  
The Central Nervous System ◽  
The Brain

As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) is predominantly found in the cytoplasm of cells in the central nervous system (CNS), suggesting its potential role in neurological disorders. Though SIRT2 is generally acknowledged to accelerate the development of neurological pathologies, it protects the brain from deterioration in certain circumstances. This review summarized the complex roles SIRT2 plays in the pathophysiology of diverse neurological disorders, compared and analyzed the discrete roles of SIRT2 in different conditions, and provided possible explanations for its paradoxical functions. In the future, the rapid growth in SIRT2 research may clarify its impacts on neurological disorders and develop therapeutic strategies targeting this protein.

AIDS and the Central Nervous System: Examining Pathobiology and Testing Therapeutic Strategies in the SIV-Infected Rhesus Monkey

1993 ◽  
Vol 693 (1 Pediatric AID) ◽  
pp. 229-244 ◽  
Author(s):  
LEE E. EIDEN ◽  
DIANNE M. RAUSCH ◽  
ANNA da CUNHA ◽  
ELISABETH A. MURRAY ◽  
MELVYN HEYES ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rhesus Monkey ◽  
Therapeutic Strategies ◽  
The Central Nervous System

scholarly journals STRUCTURAL AND FUNCTIONAL HETEROGENEITY OF ASTROCYTES IN THE BRAIN: ROLE IN NEURODEGENERATION AND NEUROINFLAMMATION

2014 ◽  
Vol 13 (5) ◽  
pp. 138-148 ◽  
Author(s):  
A. V. Morgun ◽  
N. A. Malinovskaya ◽  
Yu. K Komleva ◽  
O. L. Lopatina ◽  
N. V. Kuvacheva ◽  
...  
Keyword(s):  
Therapeutic Strategies ◽  
Functional Heterogeneity ◽  
Local Blood Flow ◽  
Metabolic Coupling ◽  
Physiological Processes ◽  
Pathogenic Factors ◽  
Structural And Functional Properties ◽  
The Central Nervous System ◽  
The Brain ◽  
Reactive Processes

The review covers the current concepts on structural and functional heterogeneity of brain astrocytes that serve for numerous (patho)physiological processes in the central nervous system. Astrocytes from various subpopulations demonstrate different sensitivity to the action of pathogenic factors, varied behaviors in reactive processes and within the local immune response. Key functions of astrocytes like neurogenesis, neuron-astroglia metabolic coupling, glial control of local blood flow greatly depend on the origin and characteristics of astroglial cells. Changes at the initial stages of neurodegeneration or in neurodevelopmental disorders are associated with significant alterations in astroglial structural and functional properties, thus suggesting new approaches to therapeutic strategies implementing astroglia-expressing molecules and targets for effective

scholarly journals New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

2020 ◽  
Author(s):  
Sarah A Neely ◽  
Jill M Williamson ◽  
Anna Klingseisen ◽  
Lida Zoupi ◽  
Jason J Early ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell ◽  
Live Imaging ◽  
Therapeutic Strategies ◽  
Demyelinating Diseases ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System

Regeneration of myelin (remyelination) in the central nervous system (CNS) has long been thought to be principally mediated by newly generated oligodendrocytes, a premise underpinning therapeutic strategies for demyelinating diseases, including multiple sclerosis (MS). Recent studies have indicated that oligodendrocytes that survive demyelination can also contribute to remyelination, including in MS, but it is unclear how remyelination by surviving oligodendrocytes compares to that of newly generated oligodendrocytes. Here we studied oligodendrocytes in MS, and also imaged remyelination in vivo by surviving and new oligodendrocytes using zebrafish. We define a previously unappreciated pathology in MS, myelination of neuronal cell bodies, which is recapitulated during remyelination by surviving oligodendrocytes in zebrafish. Live imaging also revealed that surviving oligodendrocytes make very few new sheaths, but can support sheath growth along axons. In comparison, newly made oligodendrocytes make abundant new sheaths, properly targeted to axons, and exhibit a much greater capacity for regeneration.

The variability of MR axon radii estimates in the human brain

2020 ◽  
Author(s):  
Jelle Veraart ◽  
Erika P. Raven ◽  
Luke J. Edwards ◽  
Nikolaus Weiskopf ◽  
Derek K. Jones
Keyword(s):  
Central Nervous System ◽  
Diffusion Weighted Mri ◽  
Non Invasive ◽  
Coefficient Of Variability ◽  
The Central Nervous System ◽  
Repeatability And Reproducibility ◽  
Further Development ◽  
Axonal Morphology ◽  
Neuroimaging Techniques

Abstract The noninvasive quantification of axonal morphology provides an exciting avenue to gain understanding of the function and structure of the central nervous system. Accurate non-invasive mapping of micron-sized axon radii using commonly applied neuroimaging techniques, i.e., diffusion-weighted MRI, has been bolstered by recent hardware developments. In this work, we present the whole brain characterization of the effective MR axon radius and evaluate the inter- and intra-scanner test-retest repeatability and reproducibility to promote the further development of the effective MR axon radius as a neuroimaging biomarker. We observe a coefficient-of-variability of approximately 10% in the voxelwise estimation of the effective MR radius in the test-retest analysis, but demonstrate that the performance can be improved fourfold using a customized along-tract analyses.

scholarly journals Pharmacological targeting of Tripartite Motif Containing 24 for the treatment of glioblastoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingzhi Han ◽  
Yanfei Sun
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Cancer Progression ◽  
Therapeutic Strategies ◽  
Tripartite Motif ◽  
The Central Nervous System ◽  
Series Of Experiments ◽  
Cell Propagation ◽  
Insight Into

AbstractGlioblastoma (GBM) is the most aggressive brain tumor of the central nervous system. Recent studies have reported the crucial functions of Tripartite Motif Containing 24 (TRIM24) in promoting cancer progression of GBM. However, it remains unclear if TRIM24 is an attractive druggable target for therapeutic intervention in GBM. We therefore performed a series of experiments, aiming to verify whether specific TRIM24 inhibition suppresses GBM malignant functions using dTRIM24 and IACS-9571, two novel selective TRIM24 antagonists. Our data showed that TRIM24 inhibitors serve as effective agents for inhibiting cell propagation and invasion of several patient-derived GBM stem cells (GSCs), and these effects are mediated partially through suppression of the TRIM24-SOX2 axis. This study provides novel insight into the TRIM24-based druggable dependencies, important for developing effective therapeutic strategies for brain tumors.

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