Search results: Found 8

Listing 1 - 8 of 8
Sort by
Tau oligomers

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192618 Year: Pages: 113 DOI: 10.3389/978-2-88919-261-8 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
License:

Loading...
Export citation

Choose an application

Abstract

Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer's Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a "toxic" form of tau protein. Moreover, it was suggested that a "toxic" tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, "tau oligomers" as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of "tau oligomers".

Regulation and targeting of enzymes mediating Parkinson's disease pathogenesis: focus on Parkinson's disease Kinases, GTPases and ATPases

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193998 Year: Pages: 163 DOI: 10.3389/978-2-88919-399-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
License:

Loading...
Export citation

Choose an application

Abstract

Understanding the molecular pathogenesis of Parkinson’s disease (PD) is a priority in biomedical research and a pre-requisite to improve early disease diagnosis and ultimately to developing disease-modifying strategies. In the past decade and a half, geneticists have identified several genes that are involved in the molecular pathogenesis of PD. They not only identified gene variants segregating with familial forms of PD but also genetic risk factors of sporadic PD via genome-wide association studies (GWAS). Understanding how PD genes and their gene products function holds the promise of unraveling key PD pathogenic processes. Therefore the precise cellular role of PD proteins is currently the subject of intense investigation.Interestingly, a number of PD proteins have enzymatic functions, including kinase, GTPase or ATPase functions. In the context of understanding disease pathogenesis or developing disease-modifying therapies, enzymes possess several useful features. Firstly, enzymes are often key elements of cellular signaling networks, acting as on-off switches to determine signaling intensity. For instance, kinases mediate phosphorylation events, which activate or inactivate their substrates, while GTPases modulate activity of their effector proteins via direct interaction in a GDP/GTP dependent manner. ATPases also control cellular processes through their involvement in cellular energy production and/or in transmembrane transport. Secondly, enzymes are attractive targets for therapeutics development. This is exemplified by the growing number of kinase inhibitors approved for clinical use, while compounds modulating GTPases or ATPases have also been proposed as potential therapeutics. Finally, as elements in cellular signaling networks, enzymes are not generally constitutively active but subject to further regulation through additional signaling components. Knowledge of how PD kinases, GTPases and ATPases are activated or inactivated can aid in understanding how PD signaling networks are deregulated in disease and point to new possibilities in targeting pathological signaling processes. The objective of this research topic is to provide an overview of current knowledge on the regulation of cellular signaling networks of PD kinases, GTPases and ATPases. Both upstream and downstream signaling events will be covered, with a focus on molecular events that can readily be monitored (relevance as disease biomarkers) and have a potential to be modulated (relevance as potential therapeutic target).

2015: Which new directions for Alzheimer's disease?

Author:
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195350 Year: Pages: 122 DOI: 10.3389/978-2-88919-535-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
License:

Loading...
Export citation

Choose an application

Abstract

According to the World Health Organization, more than 40 million people in the world are affected with dementia. To date, 60-70% of the cases of dementia are attributed to the Alzheimer's disease (AD). This neurodegenerative disorder gradually takes place over a period of at least 20 years before the onset of symptoms, which are impaired memory, apathy and depression. The characteristics of AD consist in neurofibrillary tangles (intraneuronal aggregates of hyperphosphorylated tau proteins) and senile plaques (dense extraneuronal deposits composed of amyloid ß (Aß)). The other features linked to these two core pathological hallmarks of AD are inflammation, oxidative stress, progressive synaptic and neuronal loss. In past years, some of the emerging therapeutic strategies against AD were employed to deal with the pathological hallmarks of the disease. Science teams all over the world try to restore the tau phosphorylation equilibrium. Their purpose is to interfere with the aggregation of tau and decrease its amount of proteins per se as well. Furthermore, they are trying either to stimulate the elimination processes of the aggregated tau proteins or to stop the formation of Aß peptides. This could be reached by the stimulation of the classic techniques of protein degradation such as the autophagic pathway, or by the targeted immunotherapy. In this Research Topic, we wish to summarize and review the etiology of AD and the related therapeutic opportunities for the next decades. To fully understand the precise mechanisms underlying AD, research findings, reviews, new insights and new approaches include AD and related tauopathies, tau phosphorylation balance, pharmacological compounds against AD, neuroprotection strategies and new therapeutic ways but also risk factors for AD and AD genetic information are included in this issue.

New Horizons in Spanish Colonial Law

Authors: --- --- --- --- et al.
Book Series: Global Perspectives on Legal History ISBN: 9783944773025 9783944773124 Year: Pages: 268 DOI: 10.12946/gplh3 Language: English
Publisher: Max Planck Institute for European Legal History
Subject: Law --- History
Added to DOAB on : 2019-04-17 11:21:03
License:

Loading...
Export citation

Choose an application

Abstract

"Spanish colonial law, derecho indiano, has since the early 20th century been a vigorous subdiscipline of legal history. One of great figures in the field, the Argentinian legal historian Víctor Tau Anzoátegui, published in 1997 his Nuevos horizontes en el estudio histórico del derecho indiano. The book, in which Tau addressed seminal methodological questions setting tone for the discipline’s future orientation, proved to be the starting point for an important renewal of the discipline. Tau drew on the writings of legal historians, such as Paolo Grossi, Antonio Manuel Hespanha, and Bartolomé Clavero. Tau emphasized the development of legal history in connection to what he called “the posture superseding rational and statutory state law.” The following features of normativity were now in need of increasing scholarly attention: the autonomy of different levels of social organization, the different modes of normative creativity, the many different notions of law and justice, the position of the jurist as an artifact of law, and the casuistic character of the legal decisions. Moreover, Tau highlighted certain areas of Spanish colonial law that he thought deserved more attention than they had hitherto received. One of these was the history of the learned jurist: the letrado was to be seen in his social, political, economic, and bureaucratic context. The Argentinian legal historian called for more scholarly works on book history, and he thought that provincial and local histories of Spanish colonial law had been studied too little.
Within the field of historical science as a whole, these ideas may not have been revolutionary, but they contributed in an important way to bringing the study of Spanish colonial law up-to-date. It is beyond doubt that Tau’s programmatic visions have been largely fulfilled in the past two decades. Equally manifest is, however, that new challenges to legal history and Spanish colonial law have emerged. The challenges of globalization are felt both in the historical and legal sciences, and not the least in the field of legal history. They have also brought major topics (back) on to the scene, such as the importance of religious normativity within the normative setting of societies. These challenges have made scholars aware of the necessity to reconstruct the circulation of ideas, juridical practices, and researchers are becoming more attentive to the intense cultural translation involved in the movement of legal ideas and institutions from one context to another. Not least, the growing consciousness and strong claims to reconsider colonial history from the premises of postcolonial scholarship expose the discipline to an unseen necessity of reconsidering its very foundational concepts. What concept of law do we need for our historical studies when considering multi-normative settings? How do we define the spatial dimension of our work? How do we analyze the entanglements in legal history?
Until recently, Spanish colonial law attracted little interest from non-Hispanic scholars, and its results were not seen within a larger global context. In this respect, Spanish colonial law was hardly different from research done on legal history of the European continent or common law. Spanish colonial law has, however, recently become a topic of interest beyond the Hispanic world. The field is now increasingly seen in the context of “global legal history,” while the old and the new research results are often put into a comparative context of both European law of the early Modern Period and other colonial legal orders.
In this volume, scholars from different parts of the Western world approach Spanish colonial law from the new perspectives of contemporary legal historical research."

Role of Natural Compounds in Inflammation and Inflammatory-Related Diseases

Author:
ISBN: 9783039215522 / 9783039215539 Year: Pages: 174 DOI: 10.3390/books978-3-03921-553-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-12-09 11:49:15
License:

Loading...
Export citation

Choose an application

Abstract

The papers reported here will contribute to proposing new insights into the mechanisms of several conditions, as well as suggesting new diagnostic alternatives and therapeutic targets in widespread pathologies such inflammation and inflammatory-based diseases. The discovery of the new is, as always, anchored in recourse to the old.

Molecular Mechanism of Alzheimer's Disease

Author:
ISBN: 9783039214075 / 9783039214082 Year: Pages: 228 DOI: 10.3390/books978-3-03921-408-2 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
License:

Loading...
Export citation

Choose an application

Abstract

Alzheimer’s disease (AD) is an age-related neurological disease that affects tens of millions of people, in addition to their carers. Hallmark features of AD include plaques composed of amyloid beta, as well as neurofibrillary tangles of tau protein. However, despite more than a century of study, the cause of Alzheimer’s disease remains unresolved. The roles of amyloid beta and tau are being questioned and other causes of AD are now under consideration. The contributions of researchers, model organisms, and various hypotheses will be examined in this Special Issue.

Keywords

?-secretase --- amyloid beta --- calcium signaling --- drug target discovery --- endoplasmic reticulum --- inositol 1,4,5-trisphosphate receptor --- ion channel --- oxidative stress --- ryanodine receptor --- therapy --- amyloid-? oligomer --- protein aggregation --- A?O receptors --- Alzheimer’s disease --- neurodegeneration --- amyloid ? --- Alzheimer’s disease --- cognitive function --- dairy products --- dementia --- inflammation --- microglia --- Alzheimer’s disease --- yeast --- Tau --- amyloid ? --- ubiquitin --- aggregation --- oligomerization --- prion --- CDK5R1 --- lncRNAs --- Alzheimer’s disease --- miR-15/107 --- NEAT1 --- HOTAIR --- MALAT1 --- heat shock response --- heat shock protein --- Alzheimer’s disease --- beta amyloid --- yeast --- Alzheimer’s disease --- complement receptor 1 --- CR1 length polymorphism --- CR1 density --- complement C3b/C4b receptor --- complement --- dementia --- molecular biology --- neurosciences --- genetic risk --- Alzheimer’s disease --- brain glucose metabolism --- neuronal differentiation --- neuronal degeneration --- Prolyl isomerases --- Pin1 --- type 2 diabetes --- type 3 diabetes --- miR-34c --- dendritic spine --- Alzheimer’s disease --- Alzheimer’s disease --- positron emission tomography (PET) --- magnetic resonance imaging (MRI) --- Alzheimer’s disease --- cystathionine-?-lyase CTH gene --- DNA methylation --- epigenetics --- epigenome-wide association study --- methylome --- methylenetetrahydrofolate reductase MTHFR gene --- nutrition --- S-adenosylmethionine --- vitamin B complex --- Alzheimer’s disease --- sleep disturbance --- sleep fragmentation --- slow-wave sleep --- amyloid beta --- tau --- proteostasis --- default-mode network --- cognitive behavioral therapy for insomnia --- APOE gene --- apolipoprotein E --- DNA methylation --- mild cognitive impairment --- Hispanics

Nonparametric Econometric Methods and Application

Author:
ISBN: 9783038979647 / 9783038979654 Year: Pages: 224 DOI: 10.3390/books978-3-03897-965-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Mathematics
Added to DOAB on : 2019-06-26 08:44:06
License:

Loading...
Export citation

Choose an application

Abstract

The present Special Issue collects a number of new contributions both at the theoretical level and in terms of applications in the areas of nonparametric and semiparametric econometric methods. In particular, this collection of papers that cover areas such as developments in local smoothing techniques, splines, series estimators, and wavelets will add to the existing rich literature on these subjects and enhance our ability to use data to test economic hypotheses in a variety of fields, such as financial economics, microeconomics, macroeconomics, labor economics, and economic growth, to name a few.

Curcumin in Health and Disease

Author:
ISBN: 9783039214495 / 9783039214501 Year: Pages: 274 DOI: 10.3390/books978-3-03921-450-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-12-09 11:49:15
License:

Loading...
Export citation

Choose an application

Abstract

The plant-derived polyphenol curcumin has been used in promoting health and combating disease for thousands of years. Its therapeutic effects have been successfully utilized in Ayurvedic and Traditional Chinese Medicine in order to treat inflammatory diseases. Current results from modern biomolecular research reveal the modulatory effects of curcumin on a variety of signal transduction pathways associated with inflammation and cancer. In this context, curcumin’s antioxidant, anti-inflammatory, anti-tumorigenic, and even anti-metastatic activities are discussed. On the cellular level, the reduced activity of several transcription factors (such as NFkB or AP-1) and the suppression of inflammatory cytokines, matrix degrading enzymes, metastasis related genes and even microRNAs are reported. On functional levels, these molecular effects translate into reduced proliferative, invasive, and metastatic capacity, as well as induced tumor cell apoptosis. All these effects have been observed not only in vitro but also in animal models. In combination with anti-neoplastic drugs like Taxol, kinase inhibitors, and radiation therapy, curcumin potentiates the drugs’ therapeutic power and can protect against undesired side effects. Natural plant-derived compounds like curcumin have one significant advantage: They do not usually cause side effects. This feature qualifies curcumin for primary prevention in healthy persons with a predisposition to cancer, arteriosclerosis, or chronic inflammatory diseases. Nonetheless, curcumin is considered safe, although potential toxic effects stemming from high dosages, long-term intake, and pharmacological interactions with other compounds have yet to be assessed. This Special Issue examines in detail and updates current research on the molecular targets, protective effects, and modes of action of natural plant-derived compounds and their roles in the prevention and treatment of human diseases.

Keywords

brain ischemia --- curcumin --- Alzheimer’s disease --- neurodegeneration --- amyloid --- tau protein --- autophagy --- mitophagy --- apoptosis --- genes --- glioblastoma multiforme --- autophagy --- mitophagy --- curcumin --- chaperone-mediated autophagy --- Akt/mTOR signaling --- transmission electron microscopy --- Curcuma longa --- turmeric tuber --- Zingiberaceae --- TLC bioautography --- antimicrobial agents --- ImageJ --- TLC-MS --- hydrostatic counter-current chromatography --- centrifugal partition chromatography --- curcumin --- death receptor --- apoptosis --- curcumin --- anticancer --- structure activity relationship --- cellular pathway --- mechanism of action --- delivery system --- wound --- wound healing --- diet --- nutrition --- micronutrients --- macronutrients --- curcumin --- amino-acids --- vitamins --- minerals --- curcumin --- oxidative metabolites --- inflamm-aging --- cancer --- metabolic reprogramming --- direct protein binding --- IL-17 --- STAT3 --- SHMT2 --- ageing --- anti-cancer --- autophagy --- microbiota --- senescence --- senolytics --- curcumin --- transthyretin --- amyloidosis --- protein aggregation --- protein misfolding --- drug discovery --- curcumin --- renal cell cancer --- tumor growth --- tumor proliferation --- cell cycling --- curcumin --- reflux esophagitis --- gastroprotection --- gastric ulcer --- Helicobacter pylori --- gastric cancer --- curcumin --- complementary medicine --- cancer treatment --- supportive care --- antioxidants --- anti-inflamation --- ulcerative colitis --- Crohn’s disease --- necrotizing enterocolitis --- curcumin --- inflammatory bowel disease --- curcumin --- silica --- chitosan --- nanoparticles --- anti-tumor --- antioxidant activity --- n/a

Listing 1 - 8 of 8
Sort by