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Articles 1 - 16 of 16
Full-Text Articles in Diseases
Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey
Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey
Dartmouth College Ph.D Dissertations
Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).
In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …
Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish
Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish
Graduate Theses, Dissertations, and Problem Reports
Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …
Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast
Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast
Senior Honors Theses
This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …
Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan
Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan
Dissertations, Theses, and Capstone Projects
Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …
The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan
Dissertations, Theses, and Capstone Projects
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.
Activity-regulated cytoskeleton-associated (Arc) …
Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak
Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak
Honors Undergraduate Theses
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …
Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford
Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford
Theses and Dissertations--Neuroscience
Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …
Hiv Tat And Morphine-Induced Neurodegeneration In A Beclin 1 Hemizygous Mouse Model, Jessica A. Lapierre
Hiv Tat And Morphine-Induced Neurodegeneration In A Beclin 1 Hemizygous Mouse Model, Jessica A. Lapierre
FIU Electronic Theses and Dissertations
Early in infection, HIV crosses the blood-brain barrier and induces neuropathology. Viral presence in the CNS coupled with secretion of neurotoxic proteins causes neuroinflammation, glial dysfunction, excitotoxicity, and neuronal death. Despite advances in combined antiretroviral therapy, HIV-infected patients present with a spectrum of cognitive and psychomotor deficits collectively referred to as HIV-associated neurological disorders (HAND). A subset of HAND patients abuses drugs such as opiates like heroin and morphine show an exacerbation and rapid progression of HIV neuropathology; however, the mechanisms of this synergy are not well understood. Autophagy is a lysosomal degradative process which eliminates and recycles cytosolic components …
Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson
Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson
Physiology Faculty Publications
Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …
Characterization Of Neuronal Specific Responses To Induced Misfolded Protein Stress In Caenorhabditis Elegans, Claire Gormley
Characterization Of Neuronal Specific Responses To Induced Misfolded Protein Stress In Caenorhabditis Elegans, Claire Gormley
Senior Honors Projects, 2010-2019
Abstract
Misfolded protein stress has been associated with many types of disease,
including neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s
disease. When a cell accumulates misfolded proteins in the endoplasmic reticulum,
misfolded protein stress occurs and the unfolded protein response (UPR) is triggered to
induce mechanisms that will allow the cell to either survive or undergo cell death. The
nascent polypeptide associated complex (NAC) is a co-translational chaperone and α/β
heterodimer that manages protein folding and localization, and protects against misfolded
protein stress; changes in NAC function have been linked to both neurodegeneration and
cancer. In these studies, I depleted …
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller
Lawrence University Honors Projects
DAF-19, the only RFX transcription factor found in C. elegans, is required for the formation of neuronal sensory cilia. Four isoforms of the DAF-19 protein have been reported, and the m86 nonsense (null) mutation affecting all four isoforms has been shown to prevent cilia formation. Transcriptome analyses employing microarrays of L1 and adult stage worms were completed using RNA from daf-19(m86) worms and an isogenic wild type strain to identify additional putative DAF-19 target genes. Using transcriptional fusions with GFP, we compared the expression patterns of several potential gene targets using fluorescence confocal microscopy. Expression patterns were characterized in …
Atypical Multisensory Integration In Niemann-Pick Type C Disease – Towards Potential Biomarkers, Gizely N. Andrade, Sophie Molholm, John S. Butler, Alice Brown Brandwein, Steven U. Walkley, John J. Foxe
Atypical Multisensory Integration In Niemann-Pick Type C Disease – Towards Potential Biomarkers, Gizely N. Andrade, Sophie Molholm, John S. Butler, Alice Brown Brandwein, Steven U. Walkley, John J. Foxe
Publications and Research
Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the …
Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes
Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes
Electronic Thesis and Dissertation Repository
Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …
Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood
Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood
Theses and Dissertations--Molecular and Cellular Biochemistry
Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …
Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen
Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen
Dissertations & Theses (Open Access)
Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild type Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. …
Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim
Dissertations & Theses (Open Access)
Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …