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Full-Text Articles in Medicine and Health Sciences
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
All ETDs from UAB
Exposure to drugs of abuse alters transcriptional programs and neuronal activity, leading to long-lasting cellular and behavioral adaptations that may contribute to addiction. The nucleus accumbens (NAc), part of the mesocorticolimbic dopamine pathway, plays a central role in motivation, reward, and reward-related learning, and this brain region is highly implicated in the development and maintenance of addiction. However, the specific contributions of defined cell populations in the NAc to drug reward processes is still poorly understood. Here, we used electrophysiological, optogenetic, and single-nucleus RNA-sequencing (snRNA-seq) approaches in a rodent model system to define the acute physiological and transcriptional responses of …
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
All ETDs from UAB
Immune dysregulation is a hallmark of various chronic lung diseases such as Chronic Obstructive Pulmonary Diseases (COPD) and Idiopathic Pulmonary Fibrosis (IPF). Previous studies in our lab have shown evidences of autoimmunity such as increases in autoantibodies, abnormal T cell profile, immune complex deposition and the presence of ectopic lymphoid structures in the lung of these patients. This thesis consolidates two separate projects about various aberrant immune responses in these diseases. The first project identified Glucose-Regulated-Protein 78 (GRP78) as the common autoantigen in COPD and characterized how GRP78 autoantibodies may increase COPD mortality via its atherogenic effects. I demonstrated that …
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
All ETDs from UAB
The renal endothelin system plays a key role in sodium excretion, particularly under high salt (HS) diet. HS stimulates renal endothelin-1 (ET-1), which binds and activates the endothelin receptor B (ETB) to excrete the excess salt. Loss of ETB receptor is linked to the development of hypertension under HS. Central clock genes are important in maintaining rhythmic patterns of sodium excretion and ET-1 is identified as a target for clock genes, including Period and Bmal1. ET-1 excretion follows a diurnal rhythm along with sodium excretion. Sexual dimorphism is evident in the diurnal regulation of endothelin-mediated natriuresis and its downstream targets. …
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
All ETDs from UAB
Acute myocardial infarction (MI) produces massive, sudden cardiomyocyte death, triggering an inflammatory and healing response that initially leads to scar formation and ultimately may induce progressive ischemic cardiomyopathy and heart failure (HF). Scar formation and left ventricular (LV) hypertrophy occur in response to MI to stabilize injury compensating for lost myocardial function. Over time, heart function can become decompensated due to neuroendocrine dysfunction and adverse LV remodeling, ultimately leading to HF. Adverse remodeling is characterized by continued dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammation. Studies have documented a resurgence in inflammatory cytokines and infiltrating leukocytes after resolution of the …
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
All ETDs from UAB
Glioblastoma multiforme (GBM) is a highly invasive, highly vascularized, and heterogeneous malignant tumor of the brain. Due to the highly infiltrative phenotype of GBM, surgery often leaves behind residual tumor cells. In many cases, recurrence occurs close to the surgical margin suggesting the role of these remaining cells in promoting tumor aggressiveness. Rapidly growing tumor creates subsequent hypoxic, and hypovascular core due to limited nutrients, whereas tumor cells in the leading edge have access to nutrients from vasculature enriched microenvironment. Studies have identified the cellular and molecular heterogeneity between the tumors in core and edge. Still, their mechanisms of intercellular …
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
All ETDs from UAB
Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies (LBs) that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is thought to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it templates the misfolding of endogenous αsyn. Identifying regulators of this process is essential to understanding how αsyn propagates and furthers disease progression. In this study, we investigated Rab27 and 14-3-3θ …
Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin
Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin
All ETDs from UAB
Hepatic Steatosis, characterized by the accumulation of triglyceride (TG) in the liver is the first stage of Alcoholic Liver Disease (ALD) and Nonalcoholic Fatty Liver Disease (NAFLD). Many metabolic pathways, including lipid metabolism, are regulated by the molecular circadian clock. Importantly, alcohol consumption and obesity induce circadian clock disruption, a risk factor for many diseases, including liver disease. In our first study, we investigated the combined effect of clock disruption and alcohol feeding on liver pathology, and diurnal rhythms in the liver molecular clock and lipid metabolism. Male liver-specific Bmal1 knockout (LKO) mice and control littermates were fed a control …
Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk
Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk
All ETDs from UAB
Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
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GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …
Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin
Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin
All ETDs from UAB
Asthma patients are increasingly presenting with asthma that is more difficult to control and treat than in years past. A subset of these patients who are sensitive to fungal species are described as having severe asthma with fungal sensitization (SAFS). Given the severity of disease, there is ever increasing interest in identifying the immune processes underlying SAFS disease pathology and the development of novel therapeutics to improve management. While sensitivity to multiple fungal species has been described in SAFS, none is more common than Aspergillus fumigatus. Here, we describe two previously unrecognized contributors to the amelioration of disease pathology in …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
All ETDs from UAB
Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
All ETDs from UAB
In the four decades since human immunodeficiency virus (HIV) was discovered, significant progress has been made in treating HIV infection and in understanding the viral and immune dynamics underlying disease pathogenesis. However, in spite of scientific advances, HIV remains a significant global health issue, and an effective preventative vaccine has yet to be created. Many groups have demonstrated the importance of CD8 T cells in viral control during natural HIV infection and believe that CD8 T cells could contribute to vaccine efficacy by alleviating disease course in individuals who became infected despite vaccination. One major obstacle to inducing potent CD8 …
C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez
C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez
All ETDs from UAB
C-reactive protein (CRP) is an evolutionarily conserved pattern recognition molecule that was first characterized for its participation in the acute phase response to bacterial infection. In the last 90 years, knowledge of CRP biology in innate immunity has expanded significantly. CRP is known to bind and activate the classical pathway of complement, to opsonize bacteria and inflamed tissue, and to modulate myeloid cell functions. CRP is normally present in the blood at low levels with its biosynthesis and serum concentration rapidly rises upon systemic inflammation. For example, high levels of serum CRP are found following acute kidney injury (AKI) in …
Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan
Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan
All ETDs from UAB
Endogenous antioxidant responses defend the lung against oxygen toxicity. In premature neonates, oxygen toxicity and impaired antioxidant defenses contribute to the development of bronchopulmonary dysplasia (BPD), the leading cause of long-term morbidity among premature infants. In adults, oxygen toxicity and impaired antioxidant defense contributes to the pathogenesis of acute lung injury (ALI). Acute Respiratory Distress Syndrome (ARDS), a severe form of ALI, can cause permeant lung damage and mortality. Our lab has established that pharmacologic thioredoxin reductase-1 (TXNRD1) inhibition attenuates lung injury in murine BPD and ALI models. The protective effects of TXNRD1 inhibition are mediated by the activation of …
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
All ETDs from UAB
The effective antibiotic pool is shrinking with antibiotic resistance a constant problem that threatens to make our current therapies obsolete. To combat this, new drug screening methodologies are required since the traditional drug screens are offering limited results or only improvements upon current treatments. This work expands upon the idea that transition metal toxicity can be preferentially targeted towards bacteria. Specifically, the focus is on copper dependent inhibitors that quickly work to eliminate Staphylococcus aureus. S. aureus is a particularly threatening bacteria with high strain variability, a litany of survival and virulence factors, and multiple drug resistance mechanisms that are …
T Cells In Synucleinopathies, Gregory Paul Williams
T Cells In Synucleinopathies, Gregory Paul Williams
All ETDs from UAB
Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …
The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman
The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman
All ETDs from UAB
Differentiation of pre-osteoblasts is critical to controlling in-vivo development and growth of bone. Recent studies highlight the importance of epigenetic regulation in directing osteoblast commitment and function. Here we show that the microRNA-23a cluster (miR-23a, 27a, and 24-2) controls bone mass in-vivo through a previously unknown epigenetic mechanism. MiR-23a cluster knockdown increased the intensity of Alkaline Phosphatase staining in MC3T3-E1 cells. Additionally, it upregulated mRNA expression of osteogenic marker genes such as Runx2 and Osteocalcin. Micro-CT analysis of 2-month and 6-month femurs showed that trabecular bone volume and trabecular number significantly increased in miR-23aClZIP mice as compared to controls. Histological …
Co-Factors In Fgf Signaling, Christopher Yanucil
Co-Factors In Fgf Signaling, Christopher Yanucil
All ETDs from UAB
The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …
The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu
All ETDs from UAB
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects over 50% of the world’s population. HCMV infection is asymptomatic in healthy individuals, however can cause severe morbidity and mortality in individuals with compromised innate or adaptive immunity. As a complex virus that has been known for about 70 years, we are still in search of vaccines or effective treatments against it. HCMV genome encodes over 175 open reading frames with the function of majority proteins remains to be defined. A unique feature of HCMV among herpesvirus is the reorganization of cellular secretory pathway and membranes to form assembly compartment (AC). …
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
All ETDs from UAB
Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian …
Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto
Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto
All ETDs from UAB
VAPB is one of three mammalian VAP proteins. It is a type-II ER transmembrane protein whose N-terminal major sperm protein domain (MSPd) is cleaved and secreted. Since the MSPd faces the cytosol, rather than the ER lumen, how it is cleaved and secreted is not yet known. In humans, P56S is a substitution mutation within the VAPB protein that segregates with cases of familial Amyotrophic Lateral Sclerosis (ALS) and prevents the secretion of VAPB MSPd. The work described in this thesis uses C. elegans to study how the N-terminal MSPd of VAPB is proteolytically processed, secreted, and regulated. C. elegans …
Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue
Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue
All ETDs from UAB
With rapidly increasing novel discoveries of associations between genomic data and complex disease phenotypes, the translation of those associations into knowledge and the identification of critical molecular mechanisms are essential to guild clinical decisions such as the diagnosis of symptomatic individuals, the prediction of disease risk, reproductive genetic counseling, and determining pharmacogenetic profiles for treatment. To decipher the genome of complex diseases, gene-centric analyses focus on detecting molecular mechanisms lead by driver genetics variants, abnormally expressed genes and high-abundance proteins through gene module construction. Additionally, the gene module construction approaches implement systems biology analysis to reveal the causative co-expressed gene …
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
All ETDs from UAB
The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …
Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni
Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni
All ETDs from UAB
Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). Maintaining low [K+]e is essential for many cellular functions including maintenance of intensely negative resting membrane potentials in the central nervous system. This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Underscoring the role of Kir4.1 in CNS functioning, genetic mutations in Kcnj10, the gene which encodes Kir4.1, causes seizures, ataxia and developmental disability in humans. Notably, loss of Kir4.1 protein and mRNA are consistently observed after CNS injury, and in a number of neurological …
Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley
Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley
All ETDs from UAB
Recent studies have identified elevated levels of a small metabolite, L-2 Hydroxyglutare (L-2HG), which curiously has no known metabolic roles. Renal tumors, hypoxia as well as larval development, specifically in Drosophila, all have been identified to have high levels of L-2HG. These broad categories suggest L-2HG has a physiological role. This work uncovers the impact of elevated levels of L-2HG in altering normal kidney and renal tumors. With structural similarity to α-Ketoglutarate (αKG), L-2HG acts as a competitive inhibitor to enzymes that utilize αKG as substrates or co-factors. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH). Loss of …
Epigenetic Regulation In Cancer And Development, Theodore Busby
Epigenetic Regulation In Cancer And Development, Theodore Busby
All ETDs from UAB
Feedback loops between cellular cues and changes in gene expression mediate the interactions between a multitude of regulatory events that promote development and cancer. Vesicular trafficking is an important process in carrying out signaling events by transporting receptors and ligands to and from the cell surface. GBF1 and BIG1 are large guanine-exchange factors (GEFs) that activate GTPase mediated shuttling of cargo through the Golgi apparatus. This dissertation demonstrates that GBF1 localizes to the cytoplasmic membrane in glioblastoma multiform cells to maintain cell shape and promote migration. Reports have shown that BIG1translocates to the nucleus is hepatocyte carcinoma cell lines in …
Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha
Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha
All ETDs from UAB
Schizophrenia (SZ) is a complex and heterogeneous mental illness in which myriad changes across multiple neurotransmitter systems (dopamine, serotonin, GABA, glutamate, and others) have been reported. Numerous regulatory mechanisms have been explored in SZ research and rather than being a disorder of one specific neurotransmitter pathway, SZ may instead be a disturbance of intracellular signaling processes that underlie the regulation of these systems. The AKT-mTOR signaling cascade plays an important role in core cellular processes of cell growth, metabolism and survival and is one such potential candidate. Abnormalities in AKT expression and activity have been consistently implicated in SZ pathophysiology …
Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho
Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho
All ETDs from UAB
In the bone marrow, Regulatory T cells (Tregs) constitute nearly 30% of CD4+ T cells, a significantly higher ratio than other tissues. Although a few of the mechanisms by which Tregs regulate normal hematopoiesis have been elucidated, our understanding of this process during leukemogenesis is ex-tremely limited. In this work, we define how Tregs maintain and support the bone marrow microenvironment. We propose that the role of Tregs extends be-yond their canonical immuno-suppressive function and that these cells are re-quired to maintain healthy hematopoiesis. We have defined tissue-specific roles for Tregs in the bone marrow including the maintenance of hematopoietic …
Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis
Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis
All ETDs from UAB
Circadian rhythms are biological processes that cycle every ~24 hours and have allowed life to adapt for optimal function across the day. These rhythms are present in all tissues in the body and are coordinated to the light/dark cycle by the suprachiasmatic nucleus (SCN) in the hypothalamus. Along with active-rest cycles, cognitive performance fluctuates across the course of the day, peaking during the active phase. In addition to the light cycle, food and meal timing can provide signaling cues to extra-SCN tissues. Food access only during the inactive phase results in weight gain and memory impairment. High fat diet protocols …
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
All ETDs from UAB
Parkinson’s disease (PD) is the most common neurogenerative motor disorder, affecting over 10 million people worldwide. Clinically, PD is diagnosed by presentation of hypokinetic movements such as bradykinesia, rigidity, and resting tremor. Additionally, PD patients have non-motor symptoms that include anosmia, constipation, and hypophonia. Current therapeutics have been successful in treating many of the locomotor symptoms, however no therapies stop or slow disease progression and the effectiveness of current medications diminishes as the symptoms invariably become more severe over the course of many years. Histopathologically, PD diagnosis is confirmed postmortem by two pathological hallmarks: 1. loss of dopaminergic neurons in …