Autophagic Dysfunction in Dementia: Scope for Development of Potential Remedies

: Dementia is a diverse category of a chronic and progressive disorder, which is commonly associated with loss of memory, difficulty in judgment, impaired language, cognitive impairment, and various other symptoms that affects a person’s daily routine life and social life. Dementia affects about 50 million people around the globe. Dementia exists in varied forms and is associated with various neurodegenerative disorders. Alzheimer's disease dementia is the most common form which accords for about 60% cases. Abnormal agglomeration of proteins in the brain has been linked to the pathogenesis of dementia. Autophagy is a necessary protein clearance mechanism, which is dependent on lysosomes. It is a basic physiological process that performs the crucial function of maintaining protein homeostasis within the cells. The autophagic dysfunction in dementia further complicates the disease by hampering the degradation and removal of abnormal pathogenic proteins. In order to understand autophagic dysfunction, it is essential to know the genetics of autophagy as well as the mutations which cause autophagic dysfunction. This understanding at the genetic level helps to define the relationship between dementia and autophagic dysfunction for developing the potential remedies for the treatment of dementia.

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Dispersion as a waste-clearance mechanism in flow through penetrating perivascular spaces in the brain

Scientific Reports ◽

10.1038/s41598-021-83951-1 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Daniel E. Troyetsky ◽

Jeffrey Tithof ◽

John H. Thomas ◽

Douglas H. Kelley

Keyword(s):

Neurodegenerative Disorders ◽

Oscillatory Flow ◽

Perivascular Spaces ◽

Advection Diffusion ◽

Circular Annulus ◽

Clearance Mechanism ◽

Flow Through ◽

The Brain ◽

Do So

AbstractAccumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer’s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-$$\beta$$ β (associated with Alzheimer’s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.

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The Relationship Between Personality and Self-Report Abilities

Journal of Individual Differences ◽

10.1027/1614-0001/a000035 ◽

2011 ◽

Vol 32 (1) ◽

pp. 47-53 ◽

Cited By ~ 6

Author(s):

Julie Aitken Schermer ◽

Andrew M. Johnson ◽

Philip A. Vernon ◽

Kerry L. Jang

Keyword(s):

Interpersonal Relationships ◽

Self Report ◽

Personality Factors ◽

Personality Factor ◽

Factor Scores ◽

Environmental Correlations ◽

Ability Factor ◽

Genetic Level ◽

The Relationship ◽

Common Environmental Factor

The relationship between self-report abilities and personality was examined at both the phenotypic (zero-order) level as well as at the genetic and environmental levels. Twins and siblings (N = 516) completed self-report ability and personality questionnaires. A factor analysis of the ability questions revealed 10 factors, including politics, interpersonal relationships, practical tasks, intellectual pursuits, academic skills, entrepreneur/business, domestic skills, vocal abilities, and creativity. Five personality factors were examined, including extraversion, conscientiousness, dependence, aggression, and openness. At the phenotypic level, the correlations between the ability factor scores and personality factor scores ranged from 0 to .60 (between political abilities and extraversion). The relationship between the two areas at the genetic level was found to range between –.01 and .60; the environmental correlations ranged from –.01 to .48. The results suggest that some of the self-report ability scores are related to self-report personality, and that some of these observed relationships may have a common genetic basis while others are from a common environmental factor.

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Grenzenlose Verantwortung

Phänomenologische Forschungen ◽

10.28937/1000107828 ◽

2010 ◽

Vol 2010 (1) ◽

pp. 5-22

Author(s):

Ralf Becker

Keyword(s):

Personal Freedom ◽

The Relationship ◽

The Brain

The article examines the relationship between freedom, guilt and responsibility in Dostojewski’s and Sartre’s works. Both attribute a great measure of personal freedom to man. Therefore, they do not tolerate excuses. Whoever is free, carries responsibility and gets caught up in guilt. Dostojewski’s focus is mainly on guilt, Sartre’s is on responsibility. They share the conviction that we can delegate responsibility for our actions or our way of living neither to a whole, of which we are a part, like society (the ,milieu'), nor to a part, for which we are the whole, like the ,brain' or the ,genes'. In that sense, Dostojewski’s and Sartre’s attempts at an ethic of responsibility also offer convincing arguments against determinism.

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EXPERIMENTAL ASSESSMENT OF THE NANOPARTICLES TOXICITY OF NICKEL OXIDE IN TWO SIZES IN THE SUBCHRONIC EXPERIMENT

ЗДОРОВЬЕ НАСЕЛЕНИЯ И СРЕДА ОБИТАНИЯ - ЗНиСО / PUBLIC HEALTH AND LIFE ENVIRONMENT ◽

10.35627/2219-5238/2018-309-12-30-35 ◽

2018 ◽

pp. 30-35

Author(s):

M.P. Sutunkova ◽

B.A. Katsnelson ◽

L.I. Privalova ◽

S.N. Solovjeva ◽

V.B. Gurvich ◽

...

Keyword(s):

Nickel Oxide ◽

Nervous Activity ◽

Equal Mass ◽

The Body ◽

Subchronic Toxicity ◽

Physiological Mechanisms ◽

Nickel Oxide Nanoparticles ◽

The Relationship ◽

The Brain ◽

Nanoparticles Toxicity

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.

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CHALLENGES OF INTERPRETATION OF GENETIC TEST RESULTS ON THE EXAMPLE OF STUDY OF ENDURANCE

SCIENCE AND SPORT: current trends ◽

10.36028/2308-8826-2020-8-1-75-82 ◽

2020 ◽

Vol 8 (1) ◽

pp. 75-82

Author(s):

Elmira Shamsuvaleeva ◽

Anastasiya Nevmyvaka ◽

Andrey Nazarenko

Keyword(s):

Sport Activity ◽

Computerized Testing ◽

Daily Routine ◽

Modern Approach ◽

Functional Studies ◽

Sport Training ◽

Genetic Test Results ◽

High Level ◽

Biomedical Education ◽

The Relationship

The purpose of the research is to study the possibility of predicting the development of aerobic endurance of athletes through a comparative analysis of the outcomes of genetic and computerized testing. Methods and organization of the research. In our research, we used scientific and methodological literature, as well as the outcomes of competitive activity and genetic analysis of a particular athlete. The total number of survey respondents was 158 people including athletes (n = 85) and coaches (n = 73). Results and discussion. Some authors find the relationship between the ability to develop and manifest endurance and the presence of the appropriate alleles of genes: ACE I, ACNT X, ACNT3 (RX, XX), ADRA2A, AMPDI C, PGC1A Gly, NFATC4, UCP2. Most studies reveal the relationship between the ACE gene and endurance supported by the I allele. Genetic foresight of the possibility of developing aerobic endurance of athletes can become the framework for the application of an individual approach in sport training, and contribute to the development of techniques aimed at the refinement of physical qualities. The modern approach to the coaching and competitive activities of athletes should include both genetic and functional studies of the human body. Conclusion. Sport forecast cannot be based solely on genetic testing results. The presence of polymorphisms in one or more genes associated with sport activity is the platform for good performance in a particular sport, but the actual manifestation of genetic predisposition depends on many factors. These factors include nutrition, daily routine and competent organization of the training process, which requires a high level of theoretical and practical competency of coaches in the field of biomedical education.

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Management of Platelets in a Persian Girl with the Tetralogy_Pantalogy of Fallot (Tof_Pof): A Case Report Study

Journal of Internal Medicine and Emergency Research ◽

10.37191/mapsci-2582-7367-1(1)-002 ◽

2020 ◽

Author(s):

Bahram Alamdary Badlou

Keyword(s):

Case Report ◽

Ventricular Septal Defect ◽

Atrial Septal Defect ◽

Sleep Disorders ◽

Social Life ◽

Rare Case ◽

Septal Defect ◽

Old Persian ◽

Underlying Mechanisms ◽

The Relationship

We report a rare case of unrepaired Tetralogy_Pantalogy of Fallot (TOF_POF) in a 20 years old Persian girl Mrs Zeynab S., who presented with cyanotic finger tops appearance, ongoing chronic thrombolytic destruction processes, and remarkable thrombocytopenia [1,2], heart ventricular septal defect (VSD), and might atrial septal defect (ASD), anxiety, sleep disorders, nightmares, and limited social life. Additionally, the relationship between underlying mechanisms, possible treatments of the thrombocytopenia, erythrocytosis, and unrepaired cardiovascular leakages remains unknown.

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Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

Current Pharmaceutical Design ◽

10.2174/1381612826666200316130128 ◽

2020 ◽

Vol 26 (13) ◽

pp. 1448-1465 ◽

Cited By ~ 1

Author(s):

Jozef Hanes ◽

Eva Dobakova ◽

Petra Majerova

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Neurodegenerative Disorders ◽

Brain Barrier ◽

Neuronal Function ◽

Brain Drug Delivery ◽

Naturally Occurring ◽

Blood Brain ◽

Traditional Approaches ◽

The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

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Polymeric Nanoparticles for Brain Drug Delivery - A Review

Current Drug Metabolism ◽

10.2174/1389200221666200508074348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 649-660

Author(s):

Subashini Raman ◽

Syed Mahmood ◽

Ayah R. Hilles ◽

Md Noushad Javed ◽

Motia Azmana ◽

...

Keyword(s):

Drug Delivery ◽

Surface Modification ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Preparation Methods ◽

Brain Drug Delivery ◽

Polymeric Nanoparticle ◽

Relationship Of ◽

The Relationship ◽

The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

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Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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