| LRRK2 Mediated Changes in TAU Phosphorylation |
Oct 2012 |
9 pages |
| Authors:
R J Nichols; PARKINSONS INST SUNNYVALE CA
|
 | The gene encoding the protein kinase LRRK2 is the most frequently mutated gene in familial Parkinson's disease (PD). The microtubule associated protein Tau is a pathological component of Alzheimer's disease and genome wide associations studies implicate Tau in PD. In several mouse models it has been shown that Tau exhibits a LRRK2 dependent change in phosphorylation status. The confluence of evidence that these two disease proteins may intersect in disease ... |
|
| Alaska Native Parkinson's Disease Registry |
Jul 2012 |
8 pages |
| Authors:
Caroline M Tanner; PARKINSONS INST SUNNYVALE CA
|
| This registry initiates a program of epidemiological assessments of PS among Alaska Native people to study the natural history and clinical management of PS, and establishes a database of Alaska native people with PS for public health, research and educational purposes. As feasible, the prevalence of PS in Alaska Native people may be estimated as well. This registry not only would facilitate future research into PS etiology, but also guide ... |
|
| Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration |
Jul 2012 |
8 pages |
| Authors:
Serge Przedborski; Vernice Jackson-Lewis; COLUMBIA UNIV NEW YORK
|
| Parkinson Disease (PD) is the second most common neurodegenerative disease of our aged population behind Alzheimer s Disease. Epidemiological, animal and cell culture studies have shown that inflammation is a part of the PD morphological picture. It has been suggested that -synuclein (a major component of the Lewy bodies present within dopamine neurons of the PD substantia nigra {SN}) is responsible for the observed inflammatory response in the PD brain. ... |
|
| Pre-Clinical Testing of New Hydroxybutyrate Analogues |
Jul 2012 |
13 pages |
| Authors:
Serge Przedborski; Vernice Jackson-Lewis; COLUMBIA UNIV NEW YORK
|
| Mitochondria are the powerplants of the cell. They produce the ATP necessary for the neurons to engage in reactions geared toward their proper function. Mitochondria contain a series of enzymes, in a chain-like array, that pass electrons along this chain via proton motive force which is initiated by complex I, the first of this series of enzymes. Complex I deficiency is considered one of the hallmarks of Parkinson s Disease ... |
|
| Validating Diagnostic and Screening Procedures for Pre-Motor Parkinson's Disease |
Apr 2012 |
7 pages |
| Authors:
J W Langston; PARKINSONS INST SUNNYVALE CA
|
| The goal of this 24-month proposal is to establish the critical infrastructure for the initiation of a five year prospective follow-up study to identify those at risk for developing PD or a related Lewy body disorder in three study populations. The ultimate goal of this work is to develop low-cost non-invasive screening methods to detect pre-motor Parkinson s disease (PD) that can be implemented population-wide. Our hypothesis is that cardiac ... |
|
| Sensory Dysfunction in Early Parkinson's Disease |
Jul 2011 |
28 pages |
| Authors:
Richard L Doty; Jacob Dubroff; Gui-Shang Ying; Thelma E McCloskey; James Wilson; Jennifer Rotz; Michele Morris; James W Hall; Neil T Shepard; Allen Osman; PENNSYLVANIA UNIV PHILADELPHIA
|
| This annual report presents the progress made, to date, in understanding the influences of early Parkinson s disease on all major sensory systems in the same subject cohort. Altered function has now been demonstrated in various sensory domains, most notably olfaction, taste, and vision. Touch and hearing appear not to be influenced by PD, although more data are needed to adequately power these elements of the study. The early sensory ... |
|
| Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration |
Jul 2010 |
16 pages |
| Authors:
Serge Przedborski; COLUMBIA UNIV NEW YORK
|
| Parkinson Disease (PD) is the second most common neurodegenerative disease of our aged population behind Alzheimer s Disease. Epidemiological, animal and cell culture studies have shown that inflammation is a part of the PD morphological picture. It has been suggested that -synuclein (a major component of the Lewy bodies present within dopamine neurons of the PD substantia nigra {SN}) is responsible for the observed inflammatory response in the PD brain. ... |
|
| Emerging Therapies in Parkinson's Disease: From Microscope to Marketplace |
Jul 2010 |
7 pages |
| Authors:
Amy Comstock-Rick; PARKINSON'S ACTION NETWORK (PAN) WASHINGTON DC
|
| On June 24, 2010 PAN hosted a panel discussion at Georgetown University featuring leading experts in the field of research. This discussion focused on the drug development pipeline, and how the different stages of drug development can work together in a better way to hasten the development of new drugs and therapies. Over 500 people from across America have viewed the Webcast to-date. We expect more people to view the ... |
|
| Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury |
Sep-2009 |
|
| Authors:
Timothy S Wells; AIR FORCE RESEARCH LAB WRIGHT-PATTERSON AFB OH
|
 | (Note: This is a progress report regarding the study. The report does not have any conclusions or results of the study.)
The objectives of this study are as follows: (1) determine the agreement between the Centers for Disease Control (CDC) definition of mild traumatic brain injury (mTBI) and the clinical judgment of a board-certified neurologist based upon medical records review; (2) utilize a historical prospective study design in a large, well-documented ... |
|
| Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate |
May-2009 |
180 pages |
| Authors:
Giselle Petzinger; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| The purpose of this proposal is to investigate the mechanisms involving pharmacological and behavioral enhanced neuroplasticity of the injured basal ganglia. Our central hypothesis is that exercise and pharmacological intervention, specifically the administration of a D2 dopamine-receptor agonist, enhances neuroplasticity by modulating glutamatedopamine interactions. This proposal has two components. Using the MPTP C57BL/6 mouse Component One will test the hypothesis that exercise enhances plasticity of the MPTP-injured basal ganglia through ... |
|
| PCBs Alter Dopamine Mediated Function in Aging Workers |
01-Jan-2008 |
14 pages |
| Authors:
Richard F Seegal; HEALTH RESEARCH INC RENSSELAER NY
|
| The major hypothesis is that prior occupational exposure to polychlorinated biphenyls (PCBs) results in decrements in neuropsychological and neurological performance and the number of dopamine (DA) terminals in the basal ganglia determined by -CIT SPECT imaging. At the conclusion of data collection 241 former capacitor workers have completed neuropsychological and neurological examinations, a comprehensive questionnaire, a blood draw to measure serum PCB and thyroid hormone concentrations, and a non-invasive test ... |
|
| Literature-Related Discovery: A Review |
05 NOV 2007 |
59 pages |
| Authors:
Ronald N. Kostoff; Joel A. Block; Jeffrey L. Solka; Michael B. Briggs; Robert L. Rushenberg; Jesse A. Stump; Dustin Johnson; Terence J. Lyons; Jeffrey R. Wyatt; OFFICE OF NAVAL RESEARCH ARLINGTON VA
|
| Discovery in science is the generation of novel, interesting, plausible, and intelligible knowledge about the objects of study. Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked to produce novel interesting, plausible, and intelligible knowledge (i.e., potential discovery). Two major variants of LRD are open discovery systems (ODS), where one starts with a problem and generates a potential solution (or vice ... |
|
| Literature-Related Discovery (LRD) |
01 NOV 2007 |
884 pages |
| Authors:
Ronald N. Kostoff; Joel A. Block; Jeffrey L. Solka; Michael B. Briggs; Robert L. Rushenberg; Jesse A. Stump; Dustin Johnson; Terence J. Lyons; Jeffrey R. Wyatt; OFFICE OF NAVAL RESEARCH ARLINGTON VA
|
| Discovery in science is the generation of novel, interesting, plausible, and intelligible knowledge about the objects of study. Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e., disjoint), in order to produce novel interesting, plausible, and intelligible knowledge (i.e., potential discovery). |
|
| Alaska Native Parkinson's Disease Registry |
NOV 2007 |
11 pages |
| Authors:
Brian A. Trimble; ALASKA NATIVE TRIBAL HEALTH CONSORTIUM ANCHORAGE AK
|
| This registry initiates a program of epidemiological assessments of PS among Alaska Natives to study the natural history and clinical management of PS and establishes a database of Alaska native people with PS for public health research and educational purposes. As feasible the prevalence of PS in Alaska Natives may be estimated as well. This registry not only would facilitate future research into PS ebology but also guide health care ... |
|
| Monitoring and Counteracting Functional Deterioration in Parkinson's Disease: A Multilevel Integrative Approach in a Primate Model System |
SEP 2007 |
23 pages |
| Authors:
Ingrid H. Philippens; Peternella S. Verhave; Marjan J. Jongsma; Erwin Blezer; Marijke A. Mol; TNO DEFENSE SECURITY AND SAFETY DELFT (NETHERLANDS)
|
| It is still largely unknown what the general course is in the progression of Parkinson's disease (PD). Presumably more than one factor is responsible. There is evidence suggesting that metabolic compromise excitotoxicity and oxidative stress are involved in the neurodegenerative process causing PD. To investigate the connection of excitotoxicity and oxidative stress with metabolic compromise in the development of the disease anti-excitotoxic treatment with riluzole and anti-oxidant treatment with EGCG ... |
|
| The Identification of Splice Variants as Molecular Markers in Parkinson's Disease |
SEP 2007 |
77 pages |
| Authors:
Gloria E. Meredith; ROSALIND FRANKLIN UNIV OF MEDICINE AND SCIENCE CHICAGO IL
|
| Alternative splicing is responsible for producing several products from a single transcript and can cause pathogenic changes in RNA in neurodegenerative disease. This proposal tests the hypothesis that regulation of normal splicing is disrupted in Parkinson's disease (PD). Scope: Experiments are designed to determine splicing products in the brain and blood of experimental MPTP models of PD and the blood of newly diagnosed PD patients, who are not yet on ... |
|
| The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease |
01 JUL 2007 |
12 pages |
| Authors:
Michael J. Zpgmond; Amanda Smith; Anthony Liou; PITTSBURGH UNIV PA
|
| Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, which is modulated by stress. We have outlined experiments to test this hypothesis in rats treated with one of several neurotoxins, beginning with 6-hydroxydopamine. Over the past year, we increased the size and training of our research team and made a number of observations of direct ... |
|
| Endoplasmic Reticulum Stress as a Mediator of Neurotoxin-Induced Dopamine Neuron Death |
JUL 2007 |
54 pages |
| Authors:
Robert E. Burke; COLUMBIA UNIV NEW YORK
|
| Programmed cell death (PCD) is an important mediator of neural degeneration in Parkinson's disease (PD). The goal of this proposal was to examine in vivo the possible role of ER stress, a mediator of PCD, in dopamine neuron death. This was done by studying mice with targeted deletions of CHOP, an upstream transcriptional mediator, and caspase-12, a downstream mediator, of ER stress-induced apoptosis. We have found that CHOP is universally ... |
|
| Neurotoxins and Neurodegenerative Disorders in Japanese-American Men Living in Hawaii |
APR 2007 |
72 pages |
| Authors:
Ross Webster G.; HAWAII UNIV HONOLULU SCHOOL OF PUBLIC HEALTH
|
| Results from the Honolulu-Asia Aging Study (HAAS) supported by this project showed Parkinson's disease (PD) risk increased with milk consumption, olfactory dysfunction, excessive daytime sleepiness, and low LDL cholesterol. Olfactory dysfunction and constipation were found to be associated with incidental Lewy bodies. A polymorphism of the MDR1 transporter gene was associated with PD. The supplement aim was to measure organochlorine levels in all brains from the HAAS archive and to ... |
|
| PCBs Alter Dopamine Mediated Function in Aging Workers |
JAN 2007 |
18 pages |
| Authors:
Richard F. Seegal; HEALTH RESEARCH INC RENSSELAER NY
|
| The major hypotheses to be tested in this project are that high-level occupational exposure of former capacitor workers to polychlorinated biphenyls (PCBs) will result in reductions in: (i) performance on neuropsychological and neurological tests that reflect the historic PCB body burden of the individual and (ii) the number of dopamine (DA) terminals in the basal ganglia. Aging former capacitor workers, previously employed at capacitor manufacturing facilities located approximately fifty miles ... |
|
| Targeting Adenosine A2A Receptors in Parkinson's Disease |
NOV 2006 |
101 pages |
| Authors:
Michael A. Schwarzschild; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| In pursuit of an improved understanding and treatment of Parkinson's disease (PD) and related neuropsychiatric disease we have held a translational research conference entitled, "Targeting Adenosine A2A Receptors in ParkThson's Disease and other CNS Disorders" in Boston, May 17-19, 2006. Recent insights into the ONS functions of the adenosine A2A receptor, A2A receptor neurotoxicology, and intriguing environmental clues have all converged to markedly enhance the potential of A2A antagonists as ... |
|
| Neuregulins, Neuroprotection and Parkinson's Disease |
SEP 2006 |
37 pages |
| Authors:
David M. Yurek; Kim B. Seroogy; KENTUCKY UNIV RESEARCH FOUNDATION LEXINGTON
|
| The main hypothesis being tested in this research project is that neuregulins, primarily focusing on glial growth factor-2 (GGF2), is neuroprotective and/or neurorestorative for the damaged dopaminergic nigrostriatal system. Other hypotheses to be tested are that GGF2 augments functional indices of the dopaminergic nigrostriatal system and that one of the intracellular signaling mechanisms mediating the protective effects of neuregulins for dopamine neurons involves the PI3-kinase pathway. These studies are being ... |
|
| Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration |
JUN 2006 |
192 pages |
| Authors:
Serge E. Przedborski; COLUMBIA UNIV NEW YORK
|
| The oxidative stress hypothesis of Parkinson's disease (PD) is thought to involve the superoxide radical and nitric oxide (NO) . It is believed that these two react with each other to produce peroxynitrite, a compound that damages cellular components in the nigrostriatal dopaminergic pathway of the brain. MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) a meperidine analog that mimics most of the hallmarks of PD, is the drug of choice for investigations into the ... |
|
| Regulated GDNF Delivery in Vivo Using Neural Stem Cells |
APR 2006 |
26 pages |
| Authors:
Clive Svendsen; WISCONSIN UNIV-MADISON
|
| This year we have published a major paper describing how hNPC-GDNF can survive and integrate into the damaged rodent brain and release GDNF for long periods. This GDNF was sufficient to induce up regulation or sprouting of dopamine neurons. We have also established that the lesion environment is crucial for both the migration and survival of transplanted cells. In our regulation studies it is clear that the single vector tTRK ... |
|
| 2006 World Parkinson Congress |
MAR 2006 |
28 pages |
| Authors:
Stanley Fahn; WORLD PARKINSON CONGRESS INC NEW YORK NY
|
| The 2006 World Parkinson Congress (WPC) was held over five days from February 22-26, 2006 in Washington, DC. It was organized to provide an international forum for the latest scientific discoveries, medical practices and caregiver initiatives related to Parkinson's disease (PD). The first-ever WPC attracted more than 3,100 attendees from nearly 60 countries who participated in 150 educational sessions over five days with speakers and audiences representing numerous disciplines. The ... |
|
| PCBs Alter Dopamine Mediated Function in Aging Workers |
JAN 2006 |
22 pages |
| Authors:
Richard F. Seegal; HEALTH RESEARCH INC RENSSELAER NY
|
| The major hypothesis is that prior occupational exposure to polychlorinated biphenyls (PCEs) results in decrements in neuropsychological and neurological performance and that these deficits are related to reductions in the number or dopamine (DA) terminals in the basal ganglia. In Albany, NY 248 former capacitor workers (62 par year) will undergo neuropsychological and neurological examinations, complete a comprehensive questionnaire, have blood drawn to measure serum thyroid hormone and PCB concentrations, ... |
|
| Neurotrophic Response to CNS Degeneration or Injury: Effects of Aging |
OCT 2005 |
40 pages |
| Authors:
David M. Yurek; Kim B. Seroogy; KENTUCKY UNIV RESEARCH FOUNDATION LEXINGTON
|
| The etiology of Parkinson's disease is not known and may be related to several factors which include inheritable mutations (genetic), exposure to environmental toxins, and/or traumatic head injury. Our current research examines age-related changes in neurotrophic factor expression in Brown Norwayl(Fischer 344 Fl hybrid (F344BNFI )rats, and we have preliminary evidence that the young and aged nigrostriatal system responds differently to neurotoxic insult or mechanical injury, i.e., young rats show ... |
|
| The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress |
14 SEP 2005 |
176 pages |
| Authors:
Bryan Yamamoto; BOSTON UNIV MA
|
| Degeneration of the nigrostriatal dopamine system is linked to the pathophysiology of Parkinson's disease. Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S. However, the neurochemical underpinnings that mediate methamphetamine toxicity and Parkinson's disease are unknown. Several variables common to methamphetamine toxicity and Parkinson's disease, each of which may be important but alone ... |
|
| Role of Mitochondrial DNA Mutations in Cellular Vulnerability to Mitochondria-Specific Environmental Toxins |
14 SEP 2005 |
17 pages |
| Authors:
Etienne C. Hirsch; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) PARIS (FRANCE)
|
| In recent years, growing evidence has shown that mutations of mitochondrial DNA (mtDNA) are an important cause of mitochondrial disorders in humans, and have been associated with common neurodegenerative disorders, aging and cancers. In line with this, it has been proposed that those mutations could genetically predispose an individual to some environmental factors thereby initiating the disease process. To test such a hypothesis in Parkinson's disease we proposed to: 1) ... |
|
| Functional Genomics of Dopaminergic Neurons and Cellular Susceptibility in Parkinson's Disease |
JUL 2005 |
10 pages |
| Authors:
Stefano Gustincich; INTERNATIONAL SCHOOL OF ADVANCED STUDIES TRIESTE (ITALY)
|
| The authors apply functional genomics techniques to describe gene expression profiles of dopaminergic neurons in the brain, with the aim of identifying the molecular basis of the vulnerability of selected classes of dopaminergic cells in Parkinson's Disease (PD). During the first year of research they have established an in-house cDNA micro-array facility with SISSA-RIKEN 20K slides that contain 2033 different full-length cDNAs encoded for secreted proteins. They also have developed ... |
|
| Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders |
JUN 2005 |
297 pages |
| Authors:
Susan E. Browne; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| The initial three years of this project determined the contributions of bioenergetic defects and oxidative stress to neurodegeneration in Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). A Consortium project, "Mitochondrial Free Radical Generation in Parkinson's Disease", was then incorporated into the grant award (2 years), to assess in vivo whether mitochondria are the source of free radical generation in animal models of Parkinson's disease (PD). Studies in the original ... |
|
| Neurotoxins and Neurodegenerative Disorders in Japanese-American Men Living in Hawaii |
APR 2005 |
10 pages |
| Authors:
G. W. Ross; PACIFIC HEALTH RESEARCH INST HONOLULU HI
|
| Pesticide exposure has been associated with increased Parkinson's disease (PD) risk. Results from the Honolulu-Asia Aging Study (HAAS) supported by this project showed PD risk doubled in individuals who worked on plantations over 20 years. Others have found high organochlorine levels in brains from decedents with PD relative to controls and dopaminergic neuron toxicity has been demonstrated in vitro but not proven in humans. This supplement aim was to measure ... |
|
| Regulated GDNF Delivery In Vivo using Neural Stem Cells |
APR 2005 |
38 pages |
| Authors:
Clive N. Svendsen; WISCONSIN UNIV-MADISON
|
| In this progress report we show that human neural progenitor cells have been grown in culture, modified to release the potent growth factor GDNP, and survive transplantation into both the rodent and primate brain. In addition we have developed new PET techniques for monitoring the brain following GDNP delivery and produced new more efficient vectors for the regulation of GDNP. We feel that this progress is leading towards the potential ... |
|
| PCBs Alter Dopamine Mediated Function in Aging Workers |
JAN 2005 |
24 pages |
| Authors:
Richard F. Seegal; HEALTH RESEARCH INC RENSSELAER NY
|
| The major hypothesis is that prior occupational exposure to polychlorinated biphenyls (PCBs) results in decrements in neuropsychological and neurological performance and that these deficits are related to reductions in the number of dopamine (DA) terminals in the basal ganglia. In Albany, NY 248 former capacitor workers (62 per year) will undergo neuropsychological and neurological examinations, complete a comprehensive questionnaire, have blood drawn to measure serum thyroid hormone and PCB concentrations, ... |
|
| Program Project on the Pathogenesis and Treatment of Parkinson's Disease |
DEC 2004 |
143 pages |
| Authors:
Serge E. Przedborski; COLUMBIA UNIV NEW YORK
|
| We are investigating the role of inflammation in, dopaminergic (DA) neuron death in the substantia nigra pars compacta (SNpc) of MPTP-treated mice. Following MPTP administration to mice, there is a robust microglial response in the SNpc that peaks earlier than the peak 0f SNpc DA neuronal death. Several enzymes are up-regulated or induced during the microglial response. Inducible nitric oxide synthase (iNOS), a principle enzyme in the synthesis of nitric ... |
|
| Neurotrophic Response to CNS Degeneration or Injury: Effects of Aging |
OCT 2004 |
36 pages |
| Authors:
David N. Yurek; KENTUCKY UNIV RESEARCH FOUNDATION LEXINGTON
|
| The etiology of Parkinson's disease is not known and may be related to several factors which include inheritable mutations (genetic), exposure to environmental toxins, and/or traumatic head injury. Our current research examines age-related changes in neurotrophic factor expression An Brown Norway/ (Fischer 344 Fl hybrid (F344BNF1)rats, and we have preliminary evidence that the young and aged nigrostriatal system responds differently to neurotoxic insult or mechanical injury, i.e., young rats show ... |
|
| Fundamental Patterns Underlying Neurotoxicity Revealed by DNA Microarray Expression Profiling |
SEP 2004 |
22 pages |
| Authors:
Karen L. O'Malley; WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
|
| The selective neurotoxins l-methyl-4-phenylpyridinium (MPP+) and 6- hydroxydopamine (6-OHDA) have been widely used to generate animal models of Parkinson's disease (PD). To understand the genetic events associated with these neurotoxins, microarray technology served to monitor differences in gene expression patterns in normal versus pathological conditions. Microarray analysis of RNA isolated from toxin treated samples revealed that the stress- induced transcription factor CHOP was dramatically up regulated by both toxins. 6-OHDA ... |
|
| Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration |
SEP 2004 |
192 pages |
| Authors:
Serge E. Przedborski; COLUMBIA UNIV NEW YORK
|
| The oxidative stress hypothesis of Parkinson's disease (PD) is thought to involve the superoxide radical and nitric oxide (NO) . It is believed that these two react with each other to produce peroxynitrite, a compound that damages cellular components in the nigrostriatal dopaminergic pathway of the brain. MPTP (l-methyl-4-phenyl-l,2,3,6- tetrahydropyridine) a meperidine analog that mimics most of the hallmarks of PD, is the drug of choice for investigations into the ... |
|
| Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction |
SEP 2004 |
11 pages |
| Authors:
Linda L. Bambrick; MARYLAND UNIV BALTIMORE
|
| This research program will determine whether accelerated neuron death due to increased oxidative stress resulting from mitochondrial dysfunction can be compensated or corrected by neurotrophin stimulation. The experiments will be carried out in two models of mitochondrial dysfunction. 1)hippocampal neurons from the trisomy 16 mouse, which undergo increased apoptosis and have a mitochondrial defect, that has now been identified as a decrease in Complex I- mediated respiration and 2)neurons chronically ... |
|
| Regulated GDNF Delivery in Vivo Using Neural Stem Cells |
APR 2004 |
17 pages |
| Authors:
Clive N. Svendsen; WISCONSIN UNIV-MADISON
|
| The major aim of this proposal was to establish lines of neural stem cells secreting GDNF under a regulatable promoter system which may be used for future transplant therapies for PD. The tasks of the first year have been met. We have changed from using rodent and monkey stem cells to using human stem cells (hNSC) due to better growth and infection profiles for human cells. We have shown that ... |
|
| Insecticide Exposure in Parkinsonism |
JAN 2004 |
36 pages |
| Authors:
Jeffrey R. Bloomquist; Bradley G. Klein; VIRGINIA POLYTECHNIC INST BLACKSBURG
|
| The EGFR receptor tyrosine kinase is dysfunctional in a wide range of solid human tumors including prostate carcinomas. The EGFR gene product is a transmembrane glycoprotein belonging to the epidermal growth factor receptor family and its cytoplasmic domain is responsible for sending the mitogenic signals into cells. We discovered that this domain of EGFR interacts with Tidl protein, a human counterparts of Drosophila tumor suppressor Tid56. Tid56 null mutation causes ... |
|
| PCBs Alter Dopamine Mediated Function in Aging Workers |
JAN 2004 |
65 pages |
| Authors:
Richard F. Seegal; HEALTH RESEARCH INC RENSSELAER NY
|
| The major hypothesis is that prior occupational exposure to polychiorinated biphenyls (PCBs) results in decrements in neuropsychological and neurological performance and reductions in the number of dopamine (DA) terminals in the basal ganglia. In Albany, NY, 248 subjects (62 per year) will undergo neuropsychological and neurological examinations, complete a comprehensive questionnaire, have blood drawn to measure serum PCB concentration and undergo a non-invasive test to determine bone lead concentrations. This ... |
|
| Role of Oligomeric a-Synuclein in Mitochondrial Membrane Permeabilization and Neurodegeneration in Parkinson's Disease |
DEC 2003 |
27 pages |
| Authors:
Sueng-Jae Lee; PARKINSONS INST SUNNYVALE CA
|
| A growing body of evidence suggests that aggregation of alpha-syn might be the fundamental cause of many neurodegenerative diseases. Several groups have developed cell culture models to study the cytotoxic effect of alpha-synuclein, and some of them indeed have observed enhanced cell death when alpha-syn, especially its mutant forms, was overexpressed. However, the link between alpha-syn aggregation and cell death has not been clearly addressed in these model systems, nor ... |
|
| Mitochondrial Mechanisms of Neuronal Injury |
NOV 2003 |
132 pages |
| Authors:
Ian J. Reynolds; PITTSBURGH UNIV PA
|
| This project is focused on understanding the mechanisms of neuronal injury in acute and chronic neurodegenerative diseases. In particular, we are interested in the role that mitochondria play in both the maintenance of neuronal viability and in the execution of neurons following injurious stimuli. Our prior studies have shown that mitochondria are an essential target for calcium overload in excitotoxic neuronal injury. We have developed a model of neuronal injury ... |
|
| Characterization of a Dopaminergic Stimulatory Factor Derived From Monoclonal Cell Lines of Striatal Origin |
OCT 2003 |
34 pages |
| Authors:
Alfred Heller; CHICAGO UNIV IL
|
| Unique dopaminergic modulatory polypeptide factors have been obtained form the lysate of an immortalized monoclonal cell derived for the mouse striatum (X61). Partially purified preparations of the lysate are capable of increasing the dopamine content of hybrid monoclonal dopaminergic cells of mesencephalic origin and preventing the loss of primary dopaminergic neurons in the absence of target cells. The monoclonal derived dopaminergic stimulatory factor has undergone a 50,000-fold purification sufficient to ... |
|
| Mechanisms of a-Synuclein Aggregation and Toxicity |
SEP 2003 |
90 pages |
| Authors:
Benjamin Wolozin; LOYOLA UNIV MAYWOOD IL
|
| ALPHA-Synuclein is a neurotoxic protein that aggregates to form pathological structures, termed Lewy bodies, in the brains of patients with Parkinson's disease. The aim of this proposal is to understand factors that stimulate or inhibit alpha-synuclein aggregation. In the second year of this proposal we investigated the sequence requirements for binding of iron to alpha- synuclein (Aim 1), the interaction of a-synuclein with different proteins and cofactors (Aim 2&3), and ... |
|
| Mechanisms of Resistance to Neurotoxins (Addendum) |
SEP 2003 |
22 pages |
| Authors:
David R. Schubert; SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA
|
| The toxicity of chemically reactive oxygen species (ROS) is thought to make a significant contribution to the death of nerve cells caused by many neurotoxins as well as in stroke and Parkinson's disease. During all of these events, some groups of nerve cells are spared relative to others. It is therefore likely that biochemical mechanisms exist which lead to increased resistance to oxidative stress and other forms of cytotoxicity. It ... |
|
| Fundamental Patterns Underlying Neurotoxicity Revealed by DNA Microarray Expression Profiling |
SEP 2003 |
32 pages |
| Authors:
Karen L. O'Malley; WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
|
| The selective neurotoxins 1-methyl-4-phenylpyribinium (MPP+) and 6- hydroxydopamine (6-OHDA) have been widely used to generate animal models of Parkinson's disease (PD). To understand the genetic events associated with these neurotoxins, microarray technology served to monitor differences in gene expression patterns in normal versus pathological conditions. Microarray analysis of RNA isolated form toxin treated samples revealed that the stress induced transcription factor CHOP was dramatically up regulated by bothe toxins. 6-OHDA ... |
|
| Placebo Controlled Study of Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease |
JUL 2003 |
9 pages |
| Authors:
Mark Hallett; NATIONAL INSTITUTES OF HEALTH BETHESDA MD
|
| During the period of the study we researched the effects of 25 Hz RTMS in 12 patients with PD. Eight rTMS sessions were performed over a four-week period. Four cortical targets were stimulated in each of the sessions (left and right motor and dorsolateral prefrontal cortex) with 300 pulses each. We haven't done any type of the interim statistical analysis of the results at this point and will not do ... |
|
| The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic, and Oxidative Stress |
JUL 2003 |
83 pages |
| Authors:
Bryan Yamamoto; BOSTON UNIV MA
|
| Degeneration of the nigrostriatal dopamine system is linked to the pathophysiology of Parkinson's disease. Similarly, the psychostimulant drug, methamphetaminealso produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U. S. However, the neurochemical underpinnings that mediate methamphetamine toxicity and Parkinson's disease are unknown. Several variables common to methamphetamine toxicity and Parkinson's disease, each of which may be important but alone ... |
|
Reports by Keyword(s)
PARKINSONS DISEASE
