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Search results for: ALZHEIMER’S DISEASE
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An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure
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SYNTHESIS OF PHOSPHORUS TACRINE ANALOGUES AS A NEW POTENTIAL ANTI-ALZHEIMER’S DISEASE AGENTS
PublicationA series of novel phosphorus tacrine derivatives was obtained in three steps, including synthesis of 9-chlorotacrine, connection of 9-chlorotacrine with hexamethylenediamine, 1,8-diaminooctane and 1,12-diaminododecane linkers and reaction of obtained tacrine diamine analogues with corresponding acid ester to give nine tacrine organophosphorus compounds. All of the obtained final structures were characterized by 1H NMR, 13C NMR,...
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Analysis of Serum of Patients With Alzheimer’s Disease for the Level of Advanced Glycation End Products
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Ovocystatin Induced Changes in Expression of Alzheimer’s Disease Relevant Proteins in APP/PS1 Transgenic Mice
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Errorless Learning as a method of neuropsychological rehabilitation of individuals suffering from dementia in the course of Alzheimer’s disease
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Design of new cholinesterase inhibitors based on phosphorus analogs of tacrine as potential anti-Alzheimer’s disease agents
PublicationBased on the analysis of the determined free binding energy (using the AutoDock Vina 1.1.2 docking program), the most potent cholinesterase inhibitors were selected. Moreover, studies of 3D visualization of the results of molecular modeling led to the identification of potential sites for the interaction of new potential inhibitors with amino acid residues building active sites of investigated cholinesterases.
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Selected mice models based on APP, MAPT and presenilin gene mutations in research on the pathogenesis of Alzheimer’s disease
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Design, synthesis and biological evaluation of novel N-phosphorylated and O-phosphorylated tacrine derivatives as potential drugs against Alzheimer’s disease
PublicationIn this work, we designed, synthesised and biologically investigated a novel series of 14N- and O-phosphorylated tacrine derivatives as potential anti-Alzheimer’s disease agents. In the reaction of 9-chlorotacrine and corresponding diamines/aminoalkylalcohol we obtained diamino and aminoalkylhydroxy tacrine derivatives. Next, the compounds were acid to give final products 6–13 and 16–21 that were characterised by 1H, 13 C, 31P...
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Rare A360T Mutation Alters GSK3β(Ser9) Binding in the Cytosolic Loop of Presenilin 1, Influencing β-Catenin Nuclear Localization and Pro-Death Gene Expression in Alzheimer’s Disease Case
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Mirosław Andrusiewicz prof. dr hab. n. med. i n. o zdr.
PeopleDiplomas, degrees conferred in specific areas ̶ Post-doctoral degree in medical sciences (doctor habilitated) (discipline: medical biology) December 4, 2017; Title of academic achievement: "Analysis of selected genes involved in the control of pathological changes in cells derived from internal female reproductive organs"; Poznan University of Medical Sciences, Faculty of Medicine II; re-viewers: Prof. Katarzyna Ziemnicka,...
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Therapeutic Potential of Multifunctional Tacrine Analogues
PublicationTacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and butyrylcholinesterase) that shows limiting clinical application by liver toxicity. In spite of this, analogues of tacrine are considered as a model inhibitor of cholinesterases in the therapy of Alzheimer’s disease. The interest in these compounds is mainly related to a high variety of their structure and biological properties. In the present review, we...
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Oxidative stress and oxidative DNA damage is characteristic for mixed Alzheimer disease/vascular dementia
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Detection of Alzheimer's disease using Otsu thresholding with tunicate swarm algorithm and deep belief network
PublicationIntroduction: Alzheimer’s Disease (AD) is a degenerative brain disorder characterized by cognitive and memory dysfunctions. The early detection of AD is necessary to reduce the mortality rate through slowing down its progression. The prevention and detection of AD is the emerging research topic for many researchers. The structural Magnetic Resonance Imaging (sMRI) is an extensively used imaging technique in detection of AD, because...
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Butyrylcholinesterase signal sequence self-aggregates and enhances amyloid fibril formation in vitro
PublicationAlzheimer’s disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and neurofibrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain Aβ plaques in AD. We have previously found that the BChE substitution in 5′UTR caused an in-frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant...
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Glucosinolates from lepidium peruvianum as potential antiamnestic drugs
PublicationLepidium peruvianum (maca) (Brassicaceae) is a naturally occurring plant mainly in the high Andes of Peru. In recent years, it has been intensively researched in terms of its influence on various diseases and towards health improvement. Alzheimer’s disease is an incurable disease that most often affects adults over the age of 60. As since 2003 the US Food and Drug Administration (FDA) did not approve any new drug for Alzheimer’s...
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Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s-like pathology in mouse and fly APP overexpression models
PublicationThe proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer’s disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models. We developed...
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Role of cholesterol in substrate recognition by -secretase
Publication-Secretase is an enzyme known to cleave multiple substrates within their transmembrane domains, with the amyloid precursor protein of Alzheimer’s Disease among the most prominent examples. The activity of -secretase strictly depends on the membrane cholesterol content, yet the mechanistic role of cholesterol in the substrate binding and cleavage remains unclear. In this work, we used all-atom molecular dynamics simulations to examine...
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Divulging the anti-acetylcholinesterase activity of Colletotrichum lentis strain KU1 extract as sustainable AChE active site inhibitors
PublicationAlzheimer’s disease (AD), also called senile dementia is a neurodegenerative disease seen commonly in the elderly and is characterised by the formation of β-amyloid plaques and neurofbrillary tangles (NFT). Though a complete understanding of the disease is lacking, recent studies showed the role of the enzyme acetylcholinesterase (AChE) in pathogenesis. Finding new lead compounds from natural sources has always been a quest for...
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Specific Binding of Cholesterol to the Amyloid Precursor Protein: Structure of the Complex and Driving Forces Characterized in Molecular Detail
PublicationC99 is the C-terminal membrane-bound fragment of the amyloid precursor protein that is cleaved by γ-secretase to release Aβ peptides, the hallmark of Alzheimer’s disease (AD). Specific interactions of C99 with cholesterol have been proposed to underlie the recognized role of cholesterol in promoting amyloidogenesis. By using molecular dynamics simulations, we studied cholesterol binding to C99 in a lipid bilayer. We determined...
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Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations
PublicationIncreasing evidence indicates a role of hyperpolarization activated cation (HCN) channels in controlling the resting membrane potential, pacemaker activity, memory formation, sleep, and arousal. Their disfunction may be associated with the development of epilepsy and age-related memory decline. Neuronal hyperexcitability involved in epileptogenesis and EEG desynchronization occur in the course of dementia in human Alzheimer’s Disease...
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Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s-like pathology in mouse and fly APP overexpression models
PublicationThe proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer’s disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models. We developed...
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Cognitive Abilities of Alzheimers Disease Transgenic Mice are Modulated by Social Context and Circadian Rhythm
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Procognitive activity of nitric oxide inhibitors and donors in animal models
PublicationNitric oxide is a small gaseous molecule that plays important roles in the majority of biological functions. Impairments of NO-related pathways contribute to the majority of neurological disorders, such as Alzheimer’s disease (AD), and mental disorders, such as schizophrenia. Cognitive decline is one of the most serious impairments accompanying both AD and schizophrenia. In the present study, the activities of NO donors, slow (spermine...
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ALZHEIMER DISEASE & ASSOCIATED DISORDERS
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Exploring the landscape of automatic cerebral microbleed detection: A comprehensive review of algorithms, current trends, and future challenges
PublicationThis paper provides the first review to date which gathers, describes, and assesses, to the best of our knowledge, all available publications on automating cerebral microbleed (CMB) detection. It provides insights into the current state of the art and highlights the challenges and opportunities in this topic. By incorporating the best practices identified in this review, we established guidelines for the development of CMB detection...
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Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB
PublicationThe olfactory bulbectomized (OBX) rat model is a well-established model of depression in which antidepressant drugs reverse deficits in the passive avoidance test 14 days after administration. Recently, the olfactory bulbectomized rat model has been proposed to be a model of Alzheimer’s disease (AD), and the available data indicate similarities between the changes that typically occur in AD and those observed in OBX animals. In...