Diseases Commons^™

The Protective Effects Of Anthocyanins On Differentiated Sh-Sy5y Cells, Abigail F. Lynn

Honors Program Projects

Background

Parkinson’s and Alzheimer’s are debilitating neurodegenerative diseases that are largely thought to be exacerbated, and perhaps even caused by oxidative stress in and around neurons. Green tea is known to contain various nutrients that reduce oxidative stress. Anthocyanins are group of nutrients that are found in plants that have red, purple, or black fruit. They have been shown to directly reduce oxidative stress and may also affect the activity of enzymes such as catalase that reduce oxidative stress. Oxidative stress can be simulated by LPS and D-galactose (DG), sugars that are commonly found on pathogens. SH-SY5Y cells are neuronal …

Correlation Between Periodontal Status And Parkinson's Disease; A Literature Review, Dragos Nicolae Ciongaru, Anca Silvia Dumitriu, Bogdan Alexandru Dimitriu, Stana Paunica, Marina Cristina Giurgiu, Brandusa Florina Mocanu, George Alexandru Popescu, Silviu Mirel Pituru

Journal of Mind and Medical Sciences

This systematic review aims to explore the relationship between chronic inflammation of periodontal disease and neurodegenerative disorders (especially Parkinson's disease), focusing primarily on pathophysiological, clinical and immunological aspects. An exhaustive search on this topic was performed in several databases (including PubMed, Scopus and Web of Science) selecting articles published between 2006 and 2023. After reviewing the titles, abstracts and protocols of each study, 13 articles were extracted for detailed assessment. The main indicators in the study included clinical signs of gingival inflammation, bleeding on probing (BoP), bone loss (BL), periodontal probing depth (PPD), and clinical attachment loss (CAL). Additionally, levels …

Plasma Glial Fibrillary Acidic Protein In Autosomal Dominant Alzheimer's Disease: Associations With Aβ-Pet, Neurodegeneration, And Cognition, Pratishtha Chatterjee, Lisa Vermunt, Brian A. Gordon, Steve Pedrini, Lynn Boonkamp, Nicola J. Armstrong, Chengjie Xiong, Abhay K. Singh, Yan Li, Hamid R. Sohrabi, Kevin Taddei, Mark Molloy, Tammie L. S. Benzinger, John C. Morris, Celeste Karch, Sarah Berman, Jasmeer Chhatwal, Carlos Cruchaga, Neill R. Graff-Radford, Gregory S. Day, Martin Farlow, Nick Fox, Alison Goate, Jason Hassenstab, Jae-Hong Lee, Johannes Levin, Eric Mcdade, Hiroshi Mori, Richard Perrin, Raquel Sanchez-Valle, Peter R. Schofield, Allan Levey, Mathias Jucker, Colin L. Masters, Anne M. Fagan, Randall J. Bateman, Ralph N. Martins, Charlotte Teunissen, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Background: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. Methods: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Results: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (A ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A -positive from A -negative ADAD …

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 …

How Alzheimer's Disease Is Taking Over (Your Brain), Hoda Aboueich

Honors Projects

As the population continues to age and the burden on our care system grows, it is urgent to understand, treat, and cure Alzheimer’s Disease (AD). Despite decades of research, there is currently no known cause for the development of dementia or AD. There are two prominent explanations currently dominant in neuroscience: amyloid plaques and neurofibrillary tangles. I will delve into the hypotheses and definitions of each of these pathologies and specifically address how they affect overall neural activity that is proposed to result in the neurodegenerative symptoms of AD. I will also discuss the recent research surrounding biomarkers, age-related neurodegeneration, …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A. Schultz, Zahra Shirzadi, Aaron P. Schultz, Lei Liu, Colleen D. Fitzpatrick, Eric Mcdade, Nicolas R. Barthelemy, Alan Renton, Bianca Esposito, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D. Chen, Alison Goate, Ricardo F. Allegri, Tammie L. S. Benzinger, Sarah Berman, Helena C. Chui, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Brian A. Gordon, Gregory S. Day, Neill R. Graff-Radford, Jason J. Hassenstab, Bernard J. Hanseeuw, Anna Hofmann, Clifford R. Jack Jr, Mathias Jucker, Celeste M. Karch, Robert A. Koeppe, Jae-Hong Lee, Allan I. Levey, Johannes Levin, Ralph Martins, Hiroshi Mori, John C. Morris, James Noble, Richard J. Perrin, Pedro Rosa-Neto, Stephen P. Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Chengjie Xiong, Keith A. Johnson, Randall J. Bateman, Reisa A. Sperling, Jasmeer P. Chhatwal, Dominantly Inherited Alzheimer Network Investigators

Research outputs 2022 to 2026

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile

Research outputs 2022 to 2026

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Microbial Influence On Alzheimer's Disease, Ashley N. Hamby

The Cardinal Edge

No abstract provided.

Characterizing The Heterogeneity Of Adult-Onset Leukoencephalopathy With Axonal Spheroids: A Digital Spatial Profiling Study, Peter Liu

Undergraduate Student Research Internships Conference

Adult-onset leukoencephalopathy with axonal spheroids (ALAS) is a group of hereditary, progressive, neurodegenerative disorders involving primarily the central nervous system white matter (WM). ALAS is characterized by patchy, asymmetrical myelin loss and axonal destruction in the WM, predominantly involving the frontoparietal regions. However, the asymmetrical and heterogenous involvement of different brain regions remains poorly characterized.

In this study, digital spatial profiling was performed to investigate the region-specific expressions of 60 proteins. Conventional immunohistochemistry methods was used validate intrepretation of probes. Using a high-plex and high-throughput method, we provide evidence of regional heterogeneity in ALAS, particularly involving key markers of microglia …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

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

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 …

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) …

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 …

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

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 …

Role Of Sarm1 In Chronic Immune-Mediated Central Nervous System Inflammation, Kenneth E. Viar Ii

Theses and Dissertations

SARM1 is an injury-induced nicotinamide adenine dinucleotide nucleosidase (NADase) that was previously shown to promote axonal degeneration in response to traumatic, toxic, and excitotoxic stressors. This raises the question of whether a SARM1-dependent program of axonal degeneration is central to a common pathway contributing to disease burden in neurological disorders. The degree to and mechanism by which SARM1 inactivation decreases the pathophysiology of such disorders is of interest to establish the rationale to pursue SARM1 as a therapeutic target. In this study, we compare the course and pathology of experimental autoimmune encephalomyelitis (EAE) in Sarm1-knockout (KO) mice and wild-type …

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

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 …

Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke

Dissertations, Master's Theses and Master's Reports

Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate’s role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative …

Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, Shankar J. Chinta, Georgia Woods, Marco Demaria, Anand Rane, Ying Zou, Amanda Mcquade, David T. Madden

Faculty Publications & Research of the TUC College of Pharmacy

Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against …

Age-Related Neurodegenerative Disease Associated Pathways Identified In Retinal And Vitreous Proteome From Human Glaucoma Eyes, M. Mirzaei, Veer Bala Gupta, J. M. Chick, T. M. Greco, Y. Wu, N. Chitranshi, R. V. Wall, Eugene Hone, L. Deng, Y. Dheer, M. Abbasi, M. Rezaeian, N. Braidy, Y. You, G. H. Salekdeh, P. A. Haynes, M. P. Molloy, Ralph Martins, I. M. Cristea, S. P. Gygi, S. L. Graham, V. K. Gupta

Research outputs 2014 to 2021

Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were …

An Isogenic Stem Cell Model Of Alzheimer's Disease: Direct Expression Of Amyloid-Beta, Teresa Marie Ubina

Electronic Theses, Projects, and Dissertations

Alzheimer’s disease (AD), identified over 100 years ago and intensively studied since the 1970s, has no effective treatments or mechanistic understanding of the underlying neurodegenerative process. Most investigators believe accumulation or aggregation of amyloid beta (Ab) proteins plays a causative role. Aβ peptides (~39-43 residues) are generated by proteolysis of the transmembrane protein APP. One reason we know so little about AD is an incomplete understanding of the cellular mechanisms responsible for Ab proteotoxicity. Human ES and iPSC models of AD are recent additions to many other models used to investigate these mechanisms. AD, however is a chronic progressive condition …

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

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 …