Novel biochemical properties of the brain ERK kinase PK40erk

1994 ◽  
Vol 15 ◽  
pp. S37
Keyword(s):  
Biochemical Properties ◽  
The Brain ◽  
Erk Kinase

scholarly journals Cilia-driven flows in the brain third ventricle

2019 ◽  
Vol 375 (1792) ◽  
pp. 20190154 ◽  
Author(s):  
Gregor Eichele ◽  
Eberhard Bodenschatz ◽  
Zuzana Ditte ◽  
Ann-Kathrin Günther ◽  
Shoba Kapoor ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Biochemical Properties ◽  
Brain Parenchyma ◽  
Ventricular Wall ◽  
Brain Ventricles ◽  
Cellular Targets ◽  
Signalling Molecules ◽  
The Third ◽  
Directional Transport ◽  
The Brain

The brain ventricles are interconnected, elaborate cavities that traverse the brain. They are filled with cerebrospinal fluid (CSF) that is, to a large part, produced by the choroid plexus, a secretory epithelium that reaches into the ventricles. CSF is rich in cytokines, growth factors and extracellular vesicles that glide along the walls of ventricles, powered by bundles of motile cilia that coat the ventricular wall. We review the cellular and biochemical properties of the ventral part of the third ventricle that is surrounded by the hypothalamus. In particular, we consider the recently discovered intricate network of cilia-driven flows that characterize this ventricle and discuss the potential physiological significance of this flow for the directional transport of CSF signals to cellular targets located either within the third ventricle or in the adjacent hypothalamic brain parenchyma. Cilia-driven streams of signalling molecules offer an exciting perspective on how fluid-borne signals are dynamically transmitted in the brain. This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.

scholarly journals The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 374 ◽  
Author(s):  
Gaber El-Saber Batiha ◽  
Amany Magdy Beshbishy ◽  
Muhammad Ikram ◽  
Zohair S. Mulla ◽  
Mohamed E. Abd El-Hack ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Biochemical Properties ◽  
Beneficial Effects ◽  
Natural Substances ◽  
Current Review ◽  
Flavonoid Quercetin ◽  
Small Intestines ◽  
The Brain

Flavonoids are a class of natural substances present in plants, fruits, vegetables, wine, bulbs, bark, stems, roots, and tea. Several attempts are being made to isolate such natural products, which are popular for their health benefits. Flavonoids are now seen as an essential component in a number of cosmetic, pharmaceutical, and medicinal formulations. Quercetin is the major polyphenolic flavonoid found in food products, including berries, apples, cauliflower, tea, cabbage, nuts, and onions that have traditionally been treated as anticancer and antiviral, and used for the treatment of allergic, metabolic, and inflammatory disorders, eye and cardiovascular diseases, and arthritis. Pharmacologically, quercetin has been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia, and Theileria parasites. Additionally, it has shown beneficial effects against Alzheimer’s disease (AD), and this activity is due to its inhibitory effect against acetylcholinesterase. It has also been documented to possess antioxidant, antifungal, anti-carcinogenic, hepatoprotective, and cytotoxic activity. Quercetin has been documented to accumulate in the lungs, liver, kidneys, and small intestines, with lower levels seen in the brain, heart, and spleen, and it is extracted through the renal, fecal, and respiratory systems. The current review examines the pharmacokinetics, as well as the toxic and biological activities of quercetin.

scholarly journals Human tauopathy-derived tau strains determine the substrates recruited for templated amplification

Brain ◽  
2021 ◽  
Author(s):  
Airi Tarutani ◽  
Haruka Miyata ◽  
Takashi Nonaka ◽  
Kazuko Hasegawa ◽  
Mari Yoshida ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Corticobasal Degeneration ◽  
Biochemical Properties ◽  
Cellular Model ◽  
Cryo Electron Microscopy ◽  
Structural Differences ◽  
The Brain ◽  
Strain Dependent ◽  
Disease Specific ◽  
Prion Hypothesis

Abstract Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Specifically, three-repeat tau and four-repeat tau in Alzheimer’s disease (AD), three-repeat tau in Pick's disease (PiD) and four-repeat in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) form amyloid-like fibrous structures that accumulate in neurons and/or glial cells. Amplification and cell-to-cell transmission of abnormal tau based on the prion hypothesis are believed to explain the onset and progression of tauopathies. Recent studies support not only the self-propagation of abnormal tau, but also the presence of conformationally distinct tau aggregates, namely tau strains. Cryo-electron microscopy analyses of patient-derived tau filaments have revealed disease-specific ordered tau structures. However, it remains unclear whether the ultrastructural and biochemical properties of tau strains are inherited during the amplification of abnormal tau in the brain. In this study, we investigated template-dependent amplification of tau aggregates using a cellular model of seeded aggregation. Tau strains extracted from human tauopathies caused strain-dependent accumulation of insoluble filamentous tau in SH-SY5Y cells. The seeding activity towards full-length four-repeat tau substrate was highest in CBD-tau seeds, followed by PSP-tau and AD-tau seeds, while AD-tau seeds showed higher seeding activity than PiD-tau seeds towards three-repeat tau substrates. Abnormal tau amplified in cells inherited the ultrastructural and biochemical properties of the original seeds. These results strongly suggest that the structural differences of patient-derived tau strains underlie the diversity of tauopathies, and that seeded aggregation and filament formation mimicking the pathogenesis of sporadic tauopathy can be reproduced in cultured cells. Our results indicate that the disease-specific conformation of tau aggregates determines the tau isoform substrate that is recruited for templated amplification, and also influences the prion-like seeding activity.

scholarly journals Molecular Cloning of cDNA for BRab from the Brain ofBombyx moriand Biochemical Properties of BRab Expressed inEscherichia coli

1998 ◽  
Vol 62 (10) ◽  
pp. 1885-1891 ◽  
Author(s):  
Tomohide UNO ◽  
Mayumi UENO ◽  
Ayumi NAKAJIMA ◽  
Yasuhito SHIRAI ◽  
Yasuo AIZONO
Keyword(s):  
Molecular Cloning ◽  
Biochemical Properties ◽  
Inescherichia Coli ◽  
The Brain

scholarly journals Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy

2017 ◽  
Vol 54 (6) ◽  
pp. 892-900 ◽  
Author(s):  
Hiroyuki Okada ◽  
Kentaro Masujin ◽  
Kohtaro Miyazawa ◽  
Yoshifumi Iwamaru ◽  
Morikazu Imamura ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Cauda Equina ◽  
Brain Homogenate ◽  
Biochemical Properties ◽  
Spongiform Encephalopathy ◽  
Infected Cattle ◽  
Atypical Form ◽  
Pathologic Features ◽  
Topographical Distribution ◽  
The Brain

H-type bovine spongiform encephalopathy (H-BSE) is an atypical form of BSE in cattle. During passaging of H-BSE in transgenic bovinized (TgBoPrP) mice, a novel phenotype of BSE, termed BSE-SW emerged and was characterized by a short incubation time and host weight loss. To investigate the biological and biochemical properties of the BSE-SW prion, a transmission study was conducted in cattle, which were inoculated intracerebrally with brain homogenate from BSE-SW–infected TgBoPrP mice. The disease incubation period was approximately 15 months. The animals showed characteristic neurological signs of dullness, and severe spongiform changes and a widespread, uniform distribution of disease-associated prion protein (PrPSc) were observed throughout the brain of infected cattle. Immunohistochemical PrPSc staining of the brain revealed the presence of intraglial accumulations and plaque-like deposits. No remarkable differences were identified in vacuolar lesion scores, topographical distribution patterns, and staining types of PrPSc in the brains of BSE-SW– vs H-BSE–infected cattle. PrPSc deposition was detected in the ganglia, vagus nerve, spinal nerve, cauda equina, adrenal medulla, and ocular muscle. Western blot analysis revealed that the specific biochemical properties of the BSE-SW prion, with an additional 10- to 12-kDa fragment, were well maintained after transmission. These findings indicated that the BSE-SW prion has biochemical properties distinct from those of H-BSE in cattle, although clinical and pathologic features of BSW-SW in cattle are indistinguishable from those of H-BSE. The results suggest that the 2 infectious agents, BSE-SW and H-BSE, are closely related strains.

Regional susceptibilities to mitochondrial dysfunctions in the CNS

2012 ◽  
Vol 393 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Milena Pinto ◽  
Alicia M. Pickrell ◽  
Carlos T. Moraes
Keyword(s):  
Mitochondrial Function ◽  
Neurological Diseases ◽  
Mitochondrial Diseases ◽  
Biochemical Properties ◽  
Specific Cell ◽  
Mitochondrial Dysfunctions ◽  
Common Features ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

Abstract Mitochondrial dysfunctions are very common features of age-related neurological diseases such as Parkinson’s, Alzheimer’s and Huntington’s disease. Several studies have shown that bioenergetic impairments have a major role in the degeneration of the central nervous system (CNS) in these patients. Accordingly, one of the main symptoms in many mitochondrial diseases is severe encephalopathy. The heterogeneity of the brain in terms of anatomic structures, cell composition, regional functions and biochemical properties makes the analysis on this organ very complex and difficult to interpret. Humans, in addition to animal models, exposed to toxins that affect mitochondrial function, in particular oxidative phosphorylation, exhibit degeneration of specific regions within the brain. Moreover, mutations in ubiquitously expressed genes that are involved in mitochondrial function also induce regional-specific cell death in the CNS. In this review, we will discuss some current hypotheses to explain the regional susceptibilities to mitochondrial dysfunctions in the CNS.

scholarly journals Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Thecla A. van Wageningen ◽  
Nelda Antonovaite ◽  
Erik Paardekam ◽  
John J. P. Brevé ◽  
Davide Iannuzzi ◽  
...  
Keyword(s):  
Gray Matter ◽  
Neurological Diseases ◽  
Biomechanical Properties ◽  
Biochemical Properties ◽  
Dynamic Indentation ◽  
Storage And Loss Moduli ◽  
Glial Cultures ◽  
Cell Elasticity ◽  
The Brain ◽  
Primary Glial Cultures

Abstract Background The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. Methods Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. Results WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. Conclusions In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.

scholarly journals Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives

2021 ◽  
Vol 22 (12) ◽  
pp. 6442
Author(s):  
Aida Kouhi ◽  
Vyshnavi Pachipulusu ◽  
Talya Kapenstein ◽  
Peisheng Hu ◽  
Alan L. Epstein ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Neurological Diseases ◽  
High Specificity ◽  
Biochemical Properties ◽  
Antibody Engineering ◽  
Stage Of Development ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Brain

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.

scholarly journals Type 1 and type 2 human PrPSc have different aggregation sizes in methionine homozygotes with sporadic, iatrogenic and variant Creutzfeldt–Jakob disease

2005 ◽  
Vol 86 (1) ◽  
pp. 237-240 ◽  
Author(s):  
Atsushi Kobayashi ◽  
Sakae Satoh ◽  
James W. Ironside ◽  
Shirou Mohri ◽  
Tetsuyuki Kitamoto
Keyword(s):  
Amyloid Plaques ◽  
Biochemical Properties ◽  
Proteinase K ◽  
Cleavage Sites ◽  
Jakob Disease ◽  
The Difference ◽  
The Brain ◽  
Codon 129

In Creutzfeldt–Jakob disease (CJD), the type (type 1 or 2) of abnormal isoform of the prion protein (PrPSc) in the brain and the genotype at codon 129 of the PrP gene are major determinants of clinicopathological phenotype. Little is known about the difference in biochemical properties between the two types of PrPSc, except for the different proteinase K cleavage sites. To investigate the size of aggregates formed by PrPSc types 1 and 2, brain homogenates from various cases of CJD with the same genotype (homozygous for methionine at codon 129) were passed through filters with a mean pore size of 72±4 nm. Type 2 PrPSc was efficiently removed from the filtrates by the filters, in contrast to type 1. Even type 2 PrPSc from a patient without amyloid plaques was removed more efficiently than type 1 from patients with amyloid plaques. These results indicate that type 2 PrPSc has a larger aggregation size than type 1, irrespective of the existence of amyloid plaques.

scholarly journals Stability of murine scrapie strain 87V after passage in sheep and comparison with the CH1641 ovine strain

2015 ◽  
Vol 96 (12) ◽  
pp. 3703-3714 ◽  
Author(s):  
Lorenzo González ◽  
Francesca Chianini ◽  
Nora Hunter ◽  
Scott Hamilton ◽  
Louise Gibbard ◽  
...  
Keyword(s):  
Prion Protein ◽  
Biochemical Properties ◽  
Survival Times ◽  
Transgenic Mouse Line ◽  
Disease Phenotypes ◽  
Brain Material ◽  
Scrapie Strain ◽  
The Stability ◽  
The Brain ◽  
Combined Data

Breed- and prion protein (PRNP) genotype-related disease phenotype variability has been observed in sheep infected with the 87V murine scrapie strain. Therefore, the stability of this strain was tested by inoculating sheep-derived 87V brain material back into VM mice. As some sheep-adapted 87V disease phenotypes were reminiscent of CH1641 scrapie, transgenic mice (Tg338) expressing ovine prion protein (PrP) were inoculated with the same sheep-derived 87V sources and with CH1641. Although at first passage in VM mice the sheep-derived 87V sources showed some divergence from the murine 87V control, all the characteristics of murine 87V infection were recovered at second passage from all sheep sources. These included 100 % attack rates and indistinguishable survival times, lesion profiles, immunohistochemical features of disease-associated PrP accumulation in the brain and PrP biochemical properties. All sheep-derived 87V sources, as well as CH1641, were transmitted to Tg338 mice with identical clinical, pathological, immunohistochemical and biochemical features. While this might potentially indicate that sheep-adapted 87V and CH1641 are the same strain, profound divergences were evident, as murine 87V was unable to infect Tg338 mice but was lethal for VM mice, while the reverse was true for CH1641. These combined data suggest that: (i) murine 87V is stable and retains its properties after passage in sheep; (ii) it can be isolated from sheep showing a CH1641-like or a more conventional scrapie phenotype; and (iii) sheep-adapted 87V scrapie, with conventional or CH1641-like phenotype, is biologically distinct from experimental CH1641 scrapie, despite the fact that they behave identically in a single transgenic mouse line.  

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