scholarly journals AβPeptide Originated from Platelets Promises New Strategy in Anti-Alzheimer’s Drug Development

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mikhail Y. Inyushin ◽  
Priscila Sanabria ◽  
Legier Rojas ◽  
Yuriy Kucheryavykh ◽  
Lilia Kucheryavykh
Keyword(s):  
Drug Development ◽  
Blood Plasma ◽  
Amyloid Beta ◽  
Blood Cells ◽  
Research Progress ◽  
Future Perspectives ◽  
Amyloid Burden ◽  
New Strategy ◽  
The Brain ◽  
Alternative Theories

The amyloid beta (Aβ) peptide and its deposits in the brain are known to be implicated in the neurodegeneration that occurs during Alzheimer’s disease (AD). Recently, alternative theories views concerning both the source of this peptide and its functions have been developed. It has been shown that, as in all other known types of amyloidosis, the production of Aβoriginates in blood cells or cells related to blood plasma, from which it can then spread from the blood to inside the brain, with the greatest concentration around brain blood vessels. In this review, we summarize research progress in this new area and outline some future perspectives. While it is still unclear whether the main source of Aβdeposits in AD is the blood, the possibility of blocking the chain of reactions that lead to constant Aβrelease from the blood to the brain may be exploited in an attempt to reduce the amyloid burden in AD. Solving the problem of Aβaccumulation in this way may provide an alternative strategy for developing anti-AD drugs.

scholarly journals Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiangpei Yue ◽  
Yanzhao Zhou ◽  
Meng Qiao ◽  
Xingnan Zhao ◽  
Xin Huang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Cognitive Functions ◽  
Memory Impairment ◽  
Amyloid Plaque ◽  
Morris Water Maze Test ◽  
Gene Expressions ◽  
App Processing ◽  
New Strategy ◽  
The Brain

Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

Recent Progress on the Drug Development for the Treatment of Alzheimer’s Disease Especially on Inhibition of Amyloid-Peptide Aggregation

2020 ◽  
Vol 20 ◽  
Author(s):  
Yuanyuan Liu ◽  
Lin Cong ◽  
Chu Han ◽  
Bo Li ◽  
Rongji Dai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Amyloid Peptide ◽  
Research Progress ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
Design And Synthesis ◽  
Aggregation Inhibitors ◽  
The Brain

: As the world's population is ageing, Alzheimer’s disease (AD) has become a big concern since patients suffering from AD have become younger and the population of AD patients is increasing worldwide. It has been revealed that the neuropathological hallmarks of AD are typically characterized by the presence of neurotoxic extracellular amyloid plaques in the brain, which are surrounded by tangles of neuronal neuronal fibers. However, the causes of AD have not been completely understood yet. Currently, there is no drug to effectively prevent AD or to completely reserve the symptoms in the patients. This article reviews the pathological features associated with AD, the recent research progress on the drug development to treat AD especially on discovery of natural product derivatives to inhibit Aβ peptide aggregation as well as design and synthesis of Aβ peptide aggregation inhibitors to treat AD.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

scholarly journals A review on the properties, reinforcing effects, and commercialization of nanomaterials for cement-based materials

2020 ◽  
Vol 9 (1) ◽  
pp. 303-322 ◽  
Author(s):  
Zhifang Zhao ◽  
Tianqi Qi ◽  
Wei Zhou ◽  
David Hui ◽  
Cong Xiao ◽  
...  
Keyword(s):  
Cement Hydration ◽  
State Of The Art ◽  
Research Progress ◽  
Market Survey ◽  
Future Perspectives ◽  
Nano Silica ◽  
Physical Processes ◽  
Existing Problems ◽  
Cement Based Materials ◽  
The Cost

AbstractThe behavior of cement-based materials is manipulated by chemical and physical processes at the nanolevel. Therefore, the application of nanomaterials in civil engineering to develop nano-modified cement-based materials is a promising research. In recent decades, a large number of researchers have tried to improve the properties of cement-based materials by employing various nanomaterials and to characterize the mechanism of nano-strengthening. In this study, the state of the art progress of nano-modified cement-based materials is systematically reviewed and summarized. First, this study reviews the basic properties and dispersion methods of nanomaterials commonly used in cement-based materials, including carbon nanotubes, carbon nanofibers, graphene, graphene oxide, nano-silica, nano-calcium carbonate, nano-calcium silicate hydrate, etc. Then the research progress on nano-engineered cementitious composites is reviewed from the view of accelerating cement hydration, reinforcing mechanical properties, and improving durability. In addition, the market and applications of nanomaterials for cement-based materials are briefly discussed, and the cost is creatively summarized through market survey. Finally, this study also summarizes the existing problems in current research and provides future perspectives accordingly.

scholarly journals Development of a New Polymeric Nanocarrier Dedicated to Controlled Clozapine Delivery at the Dopamine D2-Serotonin 5-HT1A Heteromers

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1000
Author(s):  
Sylwia Łukasiewicz
Keyword(s):  
Physicochemical Parameters ◽  
Modern Science ◽  
Dopamine D2 ◽  
Targeted Transport ◽  
First Choice ◽  
New Strategy ◽  
Cell Components ◽  
Second Generation Antipsychotic ◽  
The Brain ◽  
Polymeric Nanocarrier

Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-L-glutamic acid (PGA) and poly-L-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

Mortal Body, Immortal Mind

2012 ◽  
Vol 17 (1) ◽  
pp. 5-26
Author(s):  
Hans Goller
Keyword(s):  
Brain Activity ◽  
The Body ◽  
Activity Data ◽  
Brain Functions ◽  
Body Experiences ◽  
Research Findings ◽  
The Relationship ◽  
Near Death Experiences ◽  
The Brain ◽  
Alternative Theories

Neuroscientists keep telling us that the brain produces consciousness and consciousness does not survive brain death because it ceases when brain activity ceases. Research findings on near-death-experiences during cardiac arrest contradict this widely held conviction. They raise perplexing questions with regard to our current understanding of the relationship between consciousness and brain functions. Reports on veridical perceptions during out-of-body experiences suggest that consciousness may be experienced independently of a functioning brain and that self-consciousness may continue even after the termination of brain activity. Data on studies of near-death-experiences could be an incentive to develop alternative theories of the body-mind relation as seen in contemporary neuroscience.

Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

2009 ◽  
Vol 367 (1908) ◽  
pp. 4699-4716 ◽  
Author(s):  
Taïssia Lelekov-Boissard ◽  
Guillemette Chapuisat ◽  
Jean-Pierre Boissel ◽  
Emmanuel Grenier ◽  
Marie-Aimée Dronne
Keyword(s):  
Immune Cells ◽  
Blood Cells ◽  
Inflammatory Process ◽  
Living Cells ◽  
Therapeutic Strategies ◽  
Brain Parenchyma ◽  
Brain Cell ◽  
Cytokines And Chemokines ◽  
The Brain

The inflammatory process during stroke consists of activation of resident brain microglia and recruitment of leucocytes, namely neutrophils and monocytes/macrophages. During inflammation, microglial cells, neutrophils and macrophages secrete inflammatory cytokines and chemokines, and phagocytize dead cells. The recruitment of blood cells (neutrophils and macrophages) is mediated by the leucocyte–endothelium interactions and more specifically by cell adhesion molecules. A mathematical model is proposed to represent the dynamics of various brain cells and of immune cells (neutrophils and macrophages). This model is based on a set of six ordinary differential equations and explores the beneficial and deleterious effects of inflammation, respectively phagocytosis by immune cells and the release of pro-inflammatory mediators and nitric oxide (NO). The results of our simulations are qualitatively consistent with those observed in experiments in vivo and would suggest that the increase of phagocytosis could contribute to the increase of the percentage of living cells. The inhibition of the production of cytokines and NO and the blocking of neutrophil and macrophage infiltration into the brain parenchyma led also to the improvement of brain cell survival. This approach may help to explore the respective contributions of the beneficial and deleterious roles of the inflammatory process in stroke, and to study various therapeutic strategies in order to reduce stroke damage.

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