Nervous System Diseases Commons^™

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer

DePaul Discoveries

Reduction of stressors and anxiety levels in adolescents with chronic illnesses is a critical concept in pediatric health care in America today. The many stressors associated with chronic illness include displaying physical and mental differences, social stigma, financial difficulty, and family stress. These stressors may affect the adolescent’s ability to learn and cope in everyday life. The current research was a critical review of the literature examining studies done with adolescents coping with chronic diseases and illnesses. The aim was to analyze the most efficacious non-pharmacological methods for reducing stressors in adolescents with chronic illness. A critical review of the …

Neurotransmitter, Summer 2017, George Washington Institute For Neuroscience Neurological Institute, George Washington University Hospital

Neurotransmitter

No abstract provided.

Praja Is Overexpressed In Glioblastoma And Contributes To Neural Precursor Development, Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Lopa Mishra, Shuyun Rao, +Several Additional Authors

Medicine Faculty Publications

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the …

A Defect In Myoblast Fusion Underlies Carey-Fineman-Ziter Syndrome, S Digioia, S Connors, N. Matsunami, J Cannavino, M Rose, N Gillette, Andrea Gropman, +Several Additional Authors

Neurology Faculty Publications

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic …

Ionis Huntington’S Disease Drug A Step Closer To A Critical Phase 2 Study, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Effects Of Phosphodiesterase 3a Modulation On Murine Cerebral Microhemorrhages, Rachita K. Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and …

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 …

Join The Facebook Live Event (Soon!) On Pope Francis's Historic Audience With Huntington's Disease Families, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Light Dependent Endolysosomal Defects In A Photoreceptor Model Of Alzheimer's Disease, Michelle S. Smith

Undergraduate Honors Theses

Alzheimer’s disease (AD) is a neurodegenerative disease which is the 6^th leading cause of death in the US. AD pathology is thought to be linked to the accumulation and aggregation of toxic proteins, amyloid-beta and tau. AD development and neurodegeneration is proposed to be caused by the toxic effects of these protein accumulations, specifically amyloid-beta, as postulated by the amyloid-cascade hypothesis. To study the relationship between amyloid-beta and overall neuronal health, a study was carried out using an amyloid-expressing fruit fly photoreceptor model. Using this model, toxicity of amyloid in a stressed lysosomal system induced by light, an established …

Francis Made A Day Of ‘Superlatives’ For The Huntington's Disease Community, Says Event Co-Organizer, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Pope Francis Declares: Huntington’S Disease Should Be 'Hidden No More', Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Fear Not, Huntington’S Disease Families – Pope Francis Has Our Backs, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

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 …

Rat Hind Limb Nociceptive Withdrawal Response To Heat And Mechanical Stimuli Depends On Initial Position Of The Paw But Not Stimulus Location, Giavanna Verdi

Senior Honors Projects, 2010-2019

Mammals rapidly withdraw their hind limb in response to noxious stimulation, which is a protective movement known as the nociceptive withdrawal response (NWR). The NWR has been previously studied in spinalized, decerebrated and anesthetized non-human and human mammals; however, there is minimal information on the NWR in intact, unanesthetized non-human mammals.

The first specific aim was to identify the factors that determine the direction and magnitude of the NWR in intact, unanesthetized rats. Based on previous studies, we hypothesized that the location of stimulation and the initial position of the paw preceding the NWR will influence the direction and magnitude …

The Role Of The Expansion Segment 7 Of 25s Rrna During Oxidative Stress In Saccharomyces Cerevisiae, Ethan Gardner

Graduate School of Biomedical Sciences Theses and Dissertations

Translation is an essential process for protein expression in both eukaryotes and prokaryotes. Like any cellular process, translational factors are prone to damage when the cell is under stress. One common stressor that nearly all cells may experience is abnormal levels of reactive oxygen species (ROS). Damage caused by ROS has been associated with disease ranging from neurodegenerative impairments, to the aging process of cells. These oxygen radicals are capable of damaging a litany of molecules including nucleic acids, and molecular factors involved in translation. It has been shown that tRNA can be cleaved upon ROS-induced stress and these fragments …

Mri Analysis Of White Matter Myelin Water Content In Multiple Sclerosis: A Novel Approach Applied To Finding Correlates Of Cortical Thinning, Michael Dayan, Sandra M. Hurtado Rua, Elizabeth Monohan, Kyoko Fujimoto, Sneha Pandya, Eve M. Locastro, Tim Vartanian, Thanh D. Nguyen, Ashish Raj, Susan A. Gauthier

Mathematics and Statistics Faculty Publications

A novel lesion-mask free method based on a gamma mixture model was applied to myelin water fraction (MWF) maps to estimate the association between cortical thickness and myelin content, and how it differs between relapsing-remitting (RRMS) and secondary-progressive multiple sclerosis (SPMS) groups (135 and 23 patients, respectively). It was compared to an approach based on lesion masks. The gamma mixture distribution of whole brain, white matter (WM) MWF was characterized with three variables: the mode (most frequent value) m1 of the gamma component shown to relate to lesion, the mode m2 of the component shown to be associated with normal …

The Role Of Advanced Glycation End Products (Ages) Through The Trpa-1/Nrf-2 Activation Pathway In The Neurodegenerative Diseases, Sana Khateeb

Dissertations, Masters Theses, Capstones, and Culminating Projects

The posttranslational modification of macromolecules caused by highly reactive and toxic α-dicarbonyls, such as methylglyoxal (MGO) derived from glycolysis, is associated with various age-related diseases including diabetic complications and neurodegenerative diseases. Aging and long-term hyperglycemia causes enhanced production of this highly reactive α-dicarbonyl, which reacts with macromolecules causing irreversible damage of DNA and protein promoting the formation of advanced glycation end products (AGEs). The formation and accumulation of AGEs in different cell types affect intracellular and extracellular structure and function. AGEs can also cause macrovascular and microvascular complications through the formation of cross-links between key molecules, permanently altering cellular structure …

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system …