Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 78 for “"Neurofibrillary tangles"”.
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Investigating alterations in autophagy in Alzheimer’s disease using human brain tissue and skin-derived fibroblasts
… of abnormally phosphorylated tau protein within neurofibrillary tangles and plaques containing amyloid-β (Aβ). Autophagy is a normal intracellular mechanism that functions to degrade damaged cellular proteins. Studies have shown that there is an association between the dysfunction of the two main …
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Phosphoproteomics analysis of Alzheimer's disease
… by the appearance of amyloid-[beta] plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Despite numerous clinical trials, a limited understanding of disease pathogenesis has prevented the development of effective therapies. Several lines of genetic and …
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Molecular modeling and SAR studies of CDK5/p25 selective inhibitors
… are the formation of amyloid senile plaques and neurofibrillary tangles. Cyclin dependent kinase 5 (CDK5) is a proline directed serine/threonine kinase, which expressed primarily in the central nervous system. In the biochemical process the CDK5-natural activator, p35 is cleaved by calpain to a …
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Computational studies of tau protein : implications for the pathogenesis and treatment of neurodegenerative diseases
… constituent of protein aggregates known as neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). Previous studies suggest that tau protein may play a contributing role in neurodegenerative diseases such as AD. Thus characterizing the structural properties of tau is …
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A streptozotocin-induced model of Alzheimer's disease in mice with wild-type human tau
… of tau, the main component of neurofibrillary tangles observed in AD, leads to deficits in cell structure and function. Because recent data suggest impairments in cerebral glucose utilization and energy metabolism play a prominent role in the pathogenesis of AD, we sought to …
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Nicotinic acetylcholine receptors and their interaction with Aβ₁₋₄₂
… characterised by the post-mortem presence of neurofibrillary tangles and amyloid plaques. At present ~ 5 % of those aged over 65 years are diagnosed with AD, with this figure increasing to ~ 20 % for those aged over 75 years. It is nearly 100 years since AD was first characterised in 1907, …
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Design and Synthesis of CDK-5 and MEK-5 Inhibitors and Synthesis towards Tubulysin Analogs
… microtubule-associated protein tau, formation of neurofibrillary tangles, and possibly an acceleration of the neurodegenerative progression of Alzheimer's disease. C6-O linked benzimidazoles and C-4 benzamide and phenylacetamide benzimidazoles based on (R)-Roscovitine, a non-selective inhibitor of …
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Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro
Tau neurofibrillary tangles or aggregates are a common neuropathological feature found in a number of neurodegenerative conditions, including Alzheimer's disease. Understanding the kinetics of this aggregate build up, how it varies across patients, and how aggregation might be influenced by …
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Some aspects of biochemistry of fibrous proteins in brain
… is made of the material that forms the neurofibrillary tangles in presenile and senile dementia. Suggestions are made about the nature and origin of these diseases. Some observations are also made about the protein skeletin, but because isolation and characterization methods currently …
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Proteomic-based Signature of Brain-related Proteins as Novel Candidate Biomarkers for Alzheimer’s Disease Diagnosis
… amyloid beta deposits and intracellular neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF) where core biomarkers amyloid beta 1-42, total tau, and phosphorylated tau protein levels are changed relative to cognitively normal elderly. There is a need for …
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EPIGENETIC REGULATION IN AN IPSC-NEURON MODEL OF FAMILIAL ALZHEIMER’S DISEASE
… and accumulation of amyloid plaques and tau neurofibrillary tangles in the brain. Dysregulation of epigenetic histone modifications may lead to the expression of transcriptional programs that may play a role in disease genesis or the worsening of disease pathology. One such histone …
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Cross-Seeding Potential of Misfolded Amyloid-Beta Strains On Tau Protein: Examining The Puzzle Pieces of Alzheimer'S Disease
… (Aβ) and the intraneuronal buildup of tau neurofibrillary tangles (NFTs). Compelling evidence suggests that Aβ triggers tau accumulation. Both of these disease-associated proteins are known to contribute to the typical AD associated clinical signs. Interestingly, these proteins have been …
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Design and Synthesis of Novel Benzimidazoles and Aminothiazoles as Small Molecule Inhibitors of CDK5/p25
… hyperphosphorylation of tau protein which forms neurofibrillary tangles (NFTs), a contributing factor to the pathology of Alzheimer's disease (AD). Based on the deposited X-ray crystal structure of CDK5/p25 with a non-selective CDK inhibitor R-Roscovitine (PDB ID: 1UNL), eight series of novel …
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Homeostasis of metastable proteins in Alzheimer's disease
… set of proteins, including amyloid plaques and neurofibrillary tangles in AD. One promising avenue for progress in the field is to improve our understanding of the mechanisms by which cellular dysfunction arises from the initial protein aggregation events. The studies described in the thesis are …
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Distinct contribution of white matter damage to the clinical syndrome of Alzheimer's disease
… to be primarily due to amyloid plaques and neurofibrillary tangles. However, several other changes occur, including severe white matter damage that is yet to be fully understood. Such white matter damage includes white matter lesions (WML), which are more common in individuals with …
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Characterization of Tau Oligomeric Strains: Implications for Disease Phenotypes
… large, insoluble fibrillar structures known as neurofibrillary tangles, our lab and others found that small, oligomeric aggregates are likely the most toxic species. I found that toxic tau oligomers are elevated in progressive supranuclear palsy, traumatic brain injury and synucleinopathy models …
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Small Molecules Targeting and Modulating Toxic Tau Oligomeric Strains
… divided into two major groups: large metastable neurofibrillary tangles (NFTs) and oligomers. Recently, it has been shown that tau oligomers are highly toxic in vitro and efficient seeds for the propagation of pathology as compared to NFTs. While the toxicity of recombinant tau oligomers has been …
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Alzheimer's disease and dementia with Lewy bodies: Special focus on the role of serpins
… peptide (Abeta1-42), but also serpins, and neurofibrillary tangles of hyperphosphorylated tau protein. Pathological hallmarks of DLB include aggregates of alpha-synuclein (Lewy bodies), however, co-existing AD pathology is also frequently found. In the present work, we have investigated the …
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Design, Synthesis, & Biological Evaluation of Novel Het-Aromatic/Aromatic Analogs for the Treatment of HIV, Cancer, & Cognitive Dysfunctions
… the buildup of amyloid plaques, accumulation of neurofibrillary tangles, inflammation of the neurons, and neuronal loss leading to cognitive decline. Current drugs provide only brief symptomatic relief without modifying the underlying disease pathology. Emerging data suggest that inhibition of …
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Defining the role of heparan sulfate proteoglycans in APL-1 function in Caenorhabditis elegans
… by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The b-amyloid peptide is the major component of the plaques and is produced as a cleavage byproduct of the amyloid precursor protein (APP). APP family proteins are present in mammals and the family is considered …
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