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Search results for: ALZHEIMER'S DISEASE (AD)
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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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Investigating the disease- modifying properties of sclerotiorin in Alzheimer's therapy using acetylcholinesterase inhibition
PublicationAlzheimer's disease (AD) is a progressive neurodegenerative disorder caused due to the damage and loss of neurons in specific brain regions. It is the most common form of dementia observed in older people. The symptoms start with memory loss and gradually cause the inability to speak and do day-to-day activities. The cost of caring for those affected individuals is huge and is probably beyond most developing countries capability....
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Synthesis and Cholinesterase Inhibitory Activity of N-Phosphorylated /N-Tiophosphorylated Tacrine
PublicationNovel phosphorus and thiophosphorus tacrine derivatives were designed, synthesized and their biological activity and molecular modeling was investigated as a new potential anti-Alzheimer's disease (AD) agents. All new synthesized compound exhibited lower toxicity against neuroblastoma cell line (SH-SY5Y) in comparison with tacrine. Two analogues in the series, 7 and 9, demonstrated lack of cytotoxicity against hepatocellular cells...
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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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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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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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Genetic and Epigenetic Aspects of Atopic Dermatitis
PublicationAtopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications...
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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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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...