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Articles 1 - 12 of 12
Full-Text Articles in Nervous System Diseases
Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown
Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown
Dr Robert Brown
Genetic variants in UBQLN1 gene have been linked to neurodegeneration and mutations in UBQLN2 have recently been identified as a rare cause of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To test if genetic variants in UBQLN1 are involved in ALS. METHODS: 102 and 94 unrelated patients with familial and sporadic forms of ALS were screened for UBQLN1 gene mutations. Single nucleotide variants were further screened in a larger set of sporadic ALS (SALS) patients and unrelated control subjects using high-throughput Taqman genotyping; variants were further assessed for novelty using the 1000Genomes and NHLBI databases. In vitro studies tested the effect of …
Genetic Determinants Of Cerebral Edema In Severe Traumatic Brain Injury: A Pilot Study Of The Role Of Cacna1 And Aqp4 Gene Mutations, Raphael A. Carandang, Susanne Muehlschlegel, Wiley R. Hall, Cynthia Ouillette, Robert H. Brown Jr.
Genetic Determinants Of Cerebral Edema In Severe Traumatic Brain Injury: A Pilot Study Of The Role Of Cacna1 And Aqp4 Gene Mutations, Raphael A. Carandang, Susanne Muehlschlegel, Wiley R. Hall, Cynthia Ouillette, Robert H. Brown Jr.
Dr Robert Brown
Cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. It is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. The exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post-traumatic injury edema. Two examples are the Aquaporin-4 and CACNA1 genes, which respectively encode water and calcium channels. The Aquaporin-4 gene on chromosome 18q11.2-12.1 encodes the Aquaporin-4 protein (AQP4) water channel. AQP4 is one of the bidirectional high capacity water channels that is …
Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge
Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge
Pharmacy Faculty Articles and Research
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …
An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn
An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn
Electronic Thesis and Dissertation Repository
Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …
Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin
Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin
Dissertations & Theses (Open Access)
Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.
P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …
Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey
Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey
Senior Honors Theses
Parkinson’s disease is a motor system disorder that is caused primarily by the loss of dopamine-producing brain cells. The most affected brain structure is the pars compacta of the substantia nigra. This area of the brain is essential to the control of voluntary movement, and so its impairment leads to symptoms such as tremors, rigidity, and impaired balance. The neuronal protein alpha-synuclein has been shown to be heavily involved in the pathogenesis of the disease at the cellular level. The currently available treatments for PD mainly target dopamine regulation, and there been no cure developed for the disease at present. …
Microrna-Regulated, Systemically Delivered Raav9: A Step Closer To Cns-Restricted Transgene Expression, Jun Xie, Qing Xie, Hongwei Zhang, Stefan L. Ameres, Jui-Hung Hung, Qin Su, Ran He, Xin Mu, Seemin Seher Ahmed, Soyeon Park, Hiroki Kato, Chengjian Li, Christian Mueller, Craig C. Mello, Zhiping Weng, Terence R. Flotte, Phillip D. Zamore, Guangping Gao
Microrna-Regulated, Systemically Delivered Raav9: A Step Closer To Cns-Restricted Transgene Expression, Jun Xie, Qing Xie, Hongwei Zhang, Stefan L. Ameres, Jui-Hung Hung, Qin Su, Ran He, Xin Mu, Seemin Seher Ahmed, Soyeon Park, Hiroki Kato, Chengjian Li, Christian Mueller, Craig C. Mello, Zhiping Weng, Terence R. Flotte, Phillip D. Zamore, Guangping Gao
Christian Mueller
Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA …
Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein
Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein
Pharmacy Faculty Articles and Research
Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …
Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh
Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh
Masters Theses 1911 - February 2014
Glioblastoma is the most common malignant brain tumor, accounting for 17% of all primary brain tumors in the United States. Despite the available surgical, radiation, and chemical therapeutic options, the invasive and infiltrative nature of the tumor render current treatment options minimally effective. Recent reports have identified multiple regulators of glioblastoma progression and invasiveness. It has been demonstrated that ADAM12, A Disintegrin And Metalloproteinase encoded by ADAM12 gene, is over-expressed in glioblastoma and directly correlated with tumor proliferation. Additionally, dysregulation of the Notch signaling pathway has been implicated in the pathogenesis of many gliomas. Lastly, an evolving role of microRNAs, …
The Effect Of Load On Movement Coordination During Sled Towing, Michael Lawrence, Daniel Leib, Cara Masterson, Erin Hartigan
The Effect Of Load On Movement Coordination During Sled Towing, Michael Lawrence, Daniel Leib, Cara Masterson, Erin Hartigan
Daniel Leib
INTRODUCTION Towing sleds while walking is a popular resistance exercise for the healthy athlete. One reason for the popularity of sled towing is that it is widely believed to be a ‘functional’ exercise. Preliminary research suggests towing while walking can increases lower extremity moment impulses; however whether towing a sled utilizes the same coordination patterns as un-resisted walking is unknown. While altered patterns may not be as relevant to a healthy athlete, sled towing is also sometimes used in the rehabilitation of athletes who sustained a lower extremity injury (anterior cruciate ligament rupture) with the goal of regaining movement symmetry. …
Effects Of Fatigue On Golf Performance, Daniel J. Leib, Nicholas R. Higdon, W. Holmes Finch, Eric L. Dugan
Effects Of Fatigue On Golf Performance, Daniel J. Leib, Nicholas R. Higdon, W. Holmes Finch, Eric L. Dugan
Daniel Leib
No abstract provided.
The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler
The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler
Theses and Dissertations--Molecular and Cellular Biochemistry
Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population and is believed to be caused by the overproduction and accumulation of the toxic amyloid beta (Aβ) peptide in the brain. Aβ is produced by two separate enzymatic cleavage events of the larger membrane bound amyloid precursor protein, APP. The first, and rate-limiting, cleavage event is made by beta-secretase, or BACE1, and is thus an attractive therapeutic target. Our lab, as well as many others, has shown that BACE1 protein and activity are increased in late-stage sporadic AD. We have extended these findings to show that BACE1 …