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Novel Strategies To Modulate Synaptic Communication And Investigate The Role Of Hdac6 In Alzheimer’S Disease, Kathryne A. Medeiros
Novel Strategies To Modulate Synaptic Communication And Investigate The Role Of Hdac6 In Alzheimer’S Disease, Kathryne A. Medeiros
Doctoral Dissertations
Neuronal communication is mediated by chemical signaling at the synapse. The underlying molecular mechanisms of learning and memory are poorly understood. Very few tools are available to study how memories are formed in the mammalian brain. This dissertation focuses on developing novel strategies to study neural activity. Here we develop and use a chemical-genetic approach to enable target-specific photocontrol of inhibitory synaptic neurotransmission of GABAA receptor subtypes. The tools developed here selectively photocontrolled GABAA receptor subtypes. This enabled the investigation of the functional role these receptor subtypes have in inhibitory synaptic neurotransmission. This dissertation also focuses on identifying …
In Vitro Characterization Of Unmodified And Pyroglutamylated Alzheimer's Amyloid Beta Peptide, Jason Matos
In Vitro Characterization Of Unmodified And Pyroglutamylated Alzheimer's Amyloid Beta Peptide, Jason Matos
Electronic Theses and Dissertations
Plaques of amyloid β peptide (Aβ) are a hallmark trait of Alzheimer’s disease (AD). However, the precise role of Aβ aggregates is not well understood. Recent studies have identified that naturally occurring N-terminal truncation and pyroglutamylation of Aβ significantly increases its neurotoxicity by an unknown mechanism. Content of pyroglutamylated Aβ (pE-Aβ) in AD brains has been shown to reach up to 50% of total Aβ. Modified pE-Aβ co-aggregates with Aβ by a seeding mechanism and forms structurally distinct and highly toxic oligomers. We studied structural transitions of the full-length Aβ1-42, its pyroglutamylated form AβpE3-42, their 9:1 (Aβ1-42/AβpE3-42) and 1:1 molar …
Leptin Resistance Induced Obesity And Diabetes Promote Neuropathological Changes In The Aging Brain, Thomas Platt
Leptin Resistance Induced Obesity And Diabetes Promote Neuropathological Changes In The Aging Brain, Thomas Platt
Theses and Dissertations--Molecular and Cellular Biochemistry
The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid …
Raman Spectroscopy Of Blood Serum And Cerebrospinal Fluid And Multivariate Data Analysis For Alzheimer's Disease Diagnostics, Elena Ryzhikova
Raman Spectroscopy Of Blood Serum And Cerebrospinal Fluid And Multivariate Data Analysis For Alzheimer's Disease Diagnostics, Elena Ryzhikova
Legacy Theses & Dissertations (2009 - 2024)
The efficient and accurate diagnosis at the early stages of dementia is a key moment for effective treatment and productive research to find a new ways to combat the disease. It is especially true for Alzheimer's disease (AD) for which there is no effective cure, but several treatments are known to allow slowing down the degenerative processes. Alzheimer's disease (AD) displays only non-specific clinical symptoms of mental decline for decades after the initiation and is very challenging to differentiate even at the later stages when it becomes very aggressive. Despite the great need, current diagnostic tests are unable to diagnose …