Effects of Cystamine, a Transglutaminase Inhibitor in a Mouse Model of Progressive Supranuclear Palsy Michael Zorniak Department of Biology Lake Forest.

Slides:

Advertisements

Similar presentations

Katherine Caras Pacific Lutheran University.  Dr. Tom Carlson  Dr. Rosalind Billharz  PLU Biology Department.

Advertisements

Welgemoed Medical Centre Cape Trial Centre How does research work?

Using Gene Knockout and Transgenic Approaches to Evaluate in vivo Functions of CNS Regeneration Inhibitors: How Important is Nogo ? David Mann Tammy Hibler.

Effect of Liraglutide Treatment on Inflammation and Oxidative Stress in Young and Old APP/PS1 and WT Mice Supervisors: Dr. Christian Holscher Dr. Kerry.

ALS Research Yesterday, Today and Tomorrow Heather D. Durham, PhD.

1 Mitigating Effects of Oxidation in Aging and Diseases M. Shchepinov, R.J. Molinari *, V. Shmanai, C.Clarke, A. Manning-Bog March 5, 2010 ASENT Pipeline.

 Dominant neurodegenerative disease  Polyglutamine repeat expansions (CAG, codon, Q) in exon 1 of huntingtin gene (htt). Usually >35 CAG repeats. 

Nitric Oxide in Health, Disease, and Therapeutics NO Daniel Kim-Shapiro Department of Physics and Translational Science Center.

Comparing the Toxicity of Zinc Deficient Superoxide Dismutase (SOD) and the Quad SOD mutant: Implications for Amyotrophic Lateral Sclerosis Jesse Fitzpatrick.

OXIDATIVE STRESS. INDUCTION OF OXIDATIVE STRESS Glutathione conjugation MalnutritionMutation Phagocytic activation Tissue damageSmoking.

CSF tau Is it an informative biomarker of AD pathology Chris Clark Alzheimer’s Disease Center University of Pennsylvania.

Copper Binding of Mutant Quad SOD1

Investigation of mutated Cu/Zn Superoxide Dismutase Sam Schuberg Beckman Laboratory Howard Hughes Medical Institute: Summer 2007.

Alzheimer’s Disease Find group of ~4 students ~ 10 minutes Discuss the following personal family connection to AD (if willing only) observations/experiences.

INTRODUCTION Mutations in Presenilin (PS) 1 and 2 cause familial Alzheimer’s Disease (AD) through undetermined mechanisms. PS’s are intramembranous aspartyl.

Howard Fillit, MD Executive Director Improving Animal Trials for Alzheimer’s Disease: Recommendations for Best Practices.

Apoptosis, controlled cell death, is a natural process of development. Recently it has been found that mitochondria play an important role in apoptosis.

AMPAKINE Compounds for the Treatment of Rett Syndrome

Soluble Epoxide Hydrolase Inhibitor Reduces Neuronal Death and NF-kB Activation after Cardiac Arrest Department of Anesthesiology & Perioperative.

Parkinson’s Disease By Devin Cornford

The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. Susan A. Farr, et al.

Cells Treated with serial diluted compound and incubated for 24 hours Evaluating the Effects of Small Molecule Drugs on Correcting Alternative Splicing.

and Hippocampal Cells in Murine and Human AD Brains

The use of Pan-PPAR Agonists for Treatment of Tauopathies and Huntington’s disease Inventor: Flint Beal, MD Chairman of Neurology and Neuroscience/Neurologist-in-Chief.

Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimer’s Disease Patrick McCarthy

Effect of alternative metabolic fuels as a potential ALS therapy in mice and humans Csilla Ari, Craig R. Goldhagen, Angela Poff, Heather Held, Carol Landon,

Molecular Biology and Genetics of Amyotrophic Lateral Sclerosis Michael Sidel February 13, 2008.

Km23: a Novel Protein in the TGF  Signaling Pathway Nicole Dague Department of Biological Sciences, York College of Pennsylvania ABSTRACT An innovative.

Working for a world free of PSP & CBD Registered charity numbers: England and Wales / Scotland SC

Determining the Role of GPX, an antixodant, in the Inflammatory Changes Associated with Emphysema Navida Bholanauth Dr. Jeanine D’Armiento Columbia University.

Mounting Evidence that Endocytosis Regulates  -Synuclein Degradation Jaime Pérez Pineda Advanced Cell Biology Fall 2009.

CLINICAL AND RESEARCH MEMORY CENTER LARIBOISIERE HOSPITAL PARIS FRANCE UNIVERSITY OF PARIS DIDEROT INSERM UNIT 942 INVOLVEMENT OF PKR IN ALZHEIMER’S DISEASE.

Superoxide Dismutase and Amyotrophic Lateral Sclerosis

Effects of matrix metalloproteinase-9 on insulin survival pathways in Alzheimer’s disease Introduction Defective brain insulin signaling has been suggested.

Under the supervision of miklós jászberényi

Α-synuclein transgenic mouse models of Parkinson’s disease Michelle Maurer December 2015.

Alzheimer’s Disease: Advances and Hope Trey Sunderland, M.D. Chief, Geriatric Psychiatry Branch National Institute of Mental Health Bethesda, Maryland.

The effect of social instability stress on levels of corticosterone in the plasma of female mice KENDRA LANGRECK MENTOR: DR. MICHAEL JARCHO.

Wang Chung Han. INTRODUCTION Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a CAG expansion in the huntingtin.

Genetic enhancement of learning and memory in mice. Tang YP et al.

N deg - 1 Characteristics of neurons u Cytoskeletal organization u Microtubules and motors u Neuronal intermediate filaments u Neurofilaments u Peripherin,

Reflections on animal models of neurological disorders Marie-Francoise Chesselet UCLA

P = 0.08 Preliminary Characterization of Sleep-Wake Behavior and Locomotor Activity in the VMAT2-Deficient Mouse Model of Parkinson’s Disease Introduction.

Orexin: A possible link between diabetes and depression?

Frontotemporal dementia syndromes are united by underlying frontotemporal lobar degeneration pathology, which can be divided according to the presence.

Christian F. Krieglstein, Christoph Anthoni, Wolfgang H

PPMI in the Medical Literature

Keith A. Josephs, MD, MST, MSc Mayo Clinic Proceedings

the rat entorhinal cortex Croatian Science Foundation

Nat. Rev. Neurol. doi: /nrneurol

PERK activator decreases pathological tau species in vivo

Objectives Methods Results Conclusion

Adolescent binge ethanol exposure reduces cholinergic marker expression in the whole mouse brain. Adolescent binge ethanol exposure reduces cholinergic.

STP2 & GAPDH: Partners in crime towards -Synuclein Toxicity

Huntington's Disease: Can Mice Lead the Way to Treatment?

Boston Naming Test predicts deterioration of cerebrospinal fluid biomarkers in pre-symptomatic Alzheimer’s disease Charleen Wilder, MA, Kristina Moncrieffe,

NEUROIMAGING FINDINGS OF RARE NEURODEGENERATIVE DISEASES RELATED TO DEMENTIA SYMPTOMS INTRODUCTION: Neurodegenerative diseases are diversified group of.

Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models” by Ashleigh R. Price, Guilian Xu, Zoe B. Siemienski,

Day Two Internship Reports

Histological changes in mouse colons after DSS treatment.

Urine ammonia is highly correlated with plasma K

Neuronal ATM level is reduced in mouse models of AD

Oral administration of CX-4945 suppresses Tau phosphorylation in DYRK1A-overexpressing mice. Oral administration of CX-4945 suppresses Tau phosphorylation.

PEDF inhibits Wnt/T-cell factor/β-catenin signaling in resting and wounded skin. PEDF inhibits Wnt/T-cell factor/β-catenin signaling in resting and wounded.

Disrupted Ca2+ homeostasis enhances wild-type TDP-43 toxicity.

Spatiotemporal transmission of tau pathology from additional injection site in non-Tg mice. Spatiotemporal transmission of tau pathology from additional.

TOMA does not affect NFTs in posterior hypothalamus or cortex.

Expression of human tau in GFAP/tau Tg mice.

Subcutaneous tumor growth was significantly increased in Ogt-Tg/+ mice

Pioglitazone induces the clearance of amyloid in APP/PS1 mice.

Presentation transcript:

Effects of Cystamine, a Transglutaminase Inhibitor in a Mouse Model of Progressive Supranuclear Palsy Michael Zorniak Department of Biology Lake Forest College

Pathology Background PSP is a tauopathy Insoluble aggregates of tau in basal ganglia Transglutaminase cross-links tau Oxidative stress

Calcium TGase Tau Cross-linking Background (CH 2 ) 2 C O NH 2 H 2 NCH 2 (CH 2 ) 3 (CH 2 ) 2 C O N(CH 2 ) 4 H +NH 3 Adapted from Lorand et al., Soluble Insoluble

Previous Investigations Huntingtin Disease mice Transglutaminase cross- links huntingtin Transglutaminase enzyme activity is increased Treated with TGase inhibitor cystamine Background Halverson et al., 2005Dedeoglu et al., 2002 P301L tau transgenic mice Transglutaminase cross- links phosphorylated tau Transglutaminase enzyme activity elevated Cystamine treatment?

Effects of Cystamine NUCLEUS ER Ca 2+ TGase ROS TAU NEURONAL DEATH Cross-link P ? Hypothesis

Gaps in Knowledge Will cystamine have the same therapeutic effects in P301L mice as it did in HD mice? Predictions: Oxidative StressNeuropathology Motor Behavior

My Contribution Aim One: Determine levels of oxidative stress in P301L mice Aim Two: Treat P301L mice with cystamine and perform behavioral tests

Results kDa Actin 3 minute exposure Human AD Tissue MW + - AD

Control WT Tau P301L MW Actin 3 minute exposure 42 kDa Results ? Age (Months) Mouse Tissue

Aim 2: Effects of Cystamine Water Treated P301L Mice Cystamine Treated P301L Mice Behavioral Tests Harvest CNS Tissue Methods

Wire Hang Behavioral Test Normal Motor Disturbance Methods

Results Average Monthly Wire Hang Times for P301L Mice

Results Average Monthly Consumption for P301L Mice

Results Average Monthly Weight Gain for P301L Mice

Future Research Water vs. Cystamine Treated P301L Mice Discussion Oxidative Stress Neuropathology Motor Behavior PredictionDoneResult No Change ? ?

Acknowledgements ASPET Dr. Karie Scrogin Dr. Nancy A. Muma Shanti Frausto Nichole Dudek Ying Dai Ju Shi Bozena Zemaitaitis Funded by Society for Progressive Supranuclear Palsy