cysteine proteinase inhibitors


Summary: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.

Top Publications

  1. ncbi The cystatins: protein inhibitors of cysteine proteinases
    V Turk
    Department of Biochemistry, Jozef Stefan Institute, Ljubljana, Slovenia, Yugoslavia
    FEBS Lett 285:213-9. 1991
  2. pmc Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins
    P van Kerkhof
    Department of Cell Biology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands
    Mol Biol Cell 12:2556-66. 2001
  3. ncbi Falcipains and other cysteine proteases of malaria parasites
    Philip J Rosenthal
    Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA
    Adv Exp Med Biol 712:30-48. 2011
  4. ncbi Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis
    J Kos
    Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Ljubljana, Slovenia
    Clin Cancer Res 6:505-11. 2000
  5. ncbi Impairment of the ubiquitin-proteasome system by protein aggregation
    N F Bence
    Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
    Science 292:1552-5. 2001
  6. pmc The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion
    Alida Coppi
    Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA
    J Exp Med 201:27-33. 2005
  7. ncbi Irreversible inhibitors of serine, cysteine, and threonine proteases
    James C Powers
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332 0400, USA
    Chem Rev 102:4639-750. 2002
  8. pmc Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection
    J C Engel
    Department of Pathology, University of California San Francisco, California 94143, USA
    J Exp Med 188:725-34. 1998
  9. pmc Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies
    Karianne E Longva
    Institute of Pathology, The University of Oslo, Rikshospitalet, N 0027 Oslo, Norway
    J Cell Biol 156:843-54. 2002
  10. ncbi Functions of propeptide parts in cysteine proteases
    Bernd Wiederanders
    Institute of Biochemistry, Klinikum, Friedrich Schiller University Jena, Nonnenplan 2, D 07743 Jena, Germany
    Curr Protein Pept Sci 4:309-26. 2003

Detail Information

Publications300 found, 100 shown here

  1. ncbi The cystatins: protein inhibitors of cysteine proteinases
    V Turk
    Department of Biochemistry, Jozef Stefan Institute, Ljubljana, Slovenia, Yugoslavia
    FEBS Lett 285:213-9. 1991
  2. pmc Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins
    P van Kerkhof
    Department of Cell Biology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands
    Mol Biol Cell 12:2556-66. 2001
    ..The data suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting step of selected membrane proteins to lysosomes, thereby providing a mechanism for regulated degradation...
  3. ncbi Falcipains and other cysteine proteases of malaria parasites
    Philip J Rosenthal
    Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA
    Adv Exp Med Biol 712:30-48. 2011
    ..cysteine protease inhibitors have demonstrated potent antimalarial effects and the optimization and testing of falcipain inhibitor antimalarials is underway...
  4. ncbi Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis
    J Kos
    Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Ljubljana, Slovenia
    Clin Cancer Res 6:505-11. 2000
    The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors...
  5. ncbi Impairment of the ubiquitin-proteasome system by protein aggregation
    N F Bence
    Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
    Science 292:1552-5. 2001
  6. pmc The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion
    Alida Coppi
    Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA
    J Exp Med 201:27-33. 2005
    ..Inhibitors of CSP processing inhibit cell invasion in vitro, and treatment of mice with E-64, a highly specific cysteine protease inhibitor, completely inhibits sporozoite infectivity in vivo...
  7. ncbi Irreversible inhibitors of serine, cysteine, and threonine proteases
    James C Powers
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332 0400, USA
    Chem Rev 102:4639-750. 2002
  8. pmc Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection
    J C Engel
    Department of Pathology, University of California San Francisco, California 94143, USA
    J Exp Med 188:725-34. 1998
    ..No abnormalities were noted in the Golgi complex of host cells. This study provides proof of concept that cysteine protease inhibitors can be given at therapeutic doses to animals to selectively arrest a parasitic infection...
  9. pmc Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies
    Karianne E Longva
    Institute of Pathology, The University of Oslo, Rikshospitalet, N 0027 Oslo, Norway
    J Cell Biol 156:843-54. 2002
    ..Immuno-EM showed the localization of intact EGFR on internal membranes of MVBs. This demonstrates that the EGFR as such is not the proteasomal target...
  10. ncbi Functions of propeptide parts in cysteine proteases
    Bernd Wiederanders
    Institute of Biochemistry, Klinikum, Friedrich Schiller University Jena, Nonnenplan 2, D 07743 Jena, Germany
    Curr Protein Pept Sci 4:309-26. 2003
    ..The function of propeptides of two other important classes of cysteine peptidases - the calpains, clan CA family C4, and the caspases, clan CD family C 14 - are not considered in this review...
  11. ncbi Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum
    Puran S Sijwali
    Department of Medicine, San Francisco General Hospital, University of California San Francisco, CA 94143 0811, USA
    Mol Biochem Parasitol 150:96-106. 2006
    ..Our data suggest key roles for falcipain-2 and falcipain-3 in the development of erythrocytic malaria parasites and a complex interplay between P. falciparum cysteine and aspartic proteases...
  12. ncbi Two cysteine proteinase inhibitors from Arabidopsis thaliana, AtCYSa and AtCYSb, increasing the salt, drought, oxidation and cold tolerance
    Xinxin Zhang
    Asian Natural Environment Science Center, The University of Tokyo, Midori Cho 1 1 1, Nishitokyo City, Tokyo, Japan
    Plant Mol Biol 68:131-43. 2008
    Two cysteine proteinase inhibitors (cystatins) from Arabidopsis thaliana, designated AtCYSa and AtCYSb, were characterized. Recombinant GST-AtCYSa and GST-AtCYSb were expressed in Escherichia coli and purified...
  13. ncbi Calpain mediates progressive plasma membrane permeability and proteolysis of cytoskeleton-associated paxillin, talin, and vinculin during renal cell death
    Xiuli Liu
    Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
    J Pharmacol Exp Ther 304:63-70. 2003
    ..These results suggest that calpain mediates increased plasma membrane permeability and hydrolysis of cytoskeleton-associated paxillin, vinculin, and talin during renal cell death...
  14. pmc Matrix-independent survival of human keratinocytes through an EGF receptor/MAPK-kinase-dependent pathway
    M Jost
    Department of Dermatology and Cutaneous Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Biol Cell 12:1519-27. 2001
    ..These results demonstrate that EGFR activation contributes to anchorage-independent epithelial cell survival and identify MAPK activation as an important mechanism in this process...
  15. ncbi The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation
    Dima El-Sukkari
    The Walter and Eliza Hall Institute of Medical Research, Victoria, Melbourne, Australia
    J Immunol 171:5003-11. 2003
    ..Our results also show that CyC expression can differ markedly between closely related cell types, suggesting the existence of hitherto unrecognized mechanisms of control of CyC expression...
  16. pmc Protective mechanisms by cystatin C in neurodegenerative diseases
    Sebastien Gauthier
    Nathan S Kline Institute, Orangeburg, NY 10962, USA
    Front Biosci (Schol Ed) 3:541-54. 2011
    ..These data suggest that CysC is a therapeutic candidate that can potentially prevent brain damage and neurodegeneration...
  17. ncbi Proteinaceous cysteine protease inhibitors
    G Dubin
    Faculty of Biotechnology, Jagiellonian University, ul Gronostajowa 7, 30 387, Krakow, Poland
    Cell Mol Life Sci 62:653-69. 2005
    ..The work primarily highlights biological processes in which the inhibitors are involved and focuses on pathologies resulting from aberrant protease-inhibitor balance, pointing out emerging possibilities for their correction...
  18. ncbi Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation
    D S Campbell
    Department of Anatomy, University of Cambridge, Downing Street, CB2 3DY, Cambridge, United Kingdom
    Neuron 32:1013-26. 2001
    ..These results suggest that guidance molecules steer axon growth by triggering rapid local changes in protein levels in growth cones...
  19. pmc Characterization of the entire cystatin gene family in barley and their target cathepsin L-like cysteine-proteases, partners in the hordein mobilization during seed germination
    Manuel Martinez
    Centro de Biotecnología y Genómica de Plantas, Universidad Politecnica de Madrid, Campus Montegancedo Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcon, Madrid, Spain
    Plant Physiol 151:1531-45. 2009
    ..The opposite pattern of transcription expression in gibberellin-treated aleurones presented by inhibitors and enzymes allowed proteases to specifically degrade B, C, and D hordeins stored in the endosperm of barley seeds...
  20. pmc Murine cytomegalovirus m38.5 protein inhibits Bax-mediated cell death
    Igor Jurak
    Division of Viral Infections, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany
    J Virol 82:4812-22. 2008
    ..Moreover, the fact that MCMV-infected cells are protected from both Bak- and Bax-mediated cell death suggests that MCMV possesses an additional, as-yet-unidentified mechanism to block Bak-mediated apoptosis...
  21. ncbi Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7
    M Yokouchi
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 274:31707-12. 1999
    ..This mechanism participates in the down-regulation of tyrosine kinase receptors and loss of this function, as occurs in the naturally occurring 70Z-Cbl isoform, probably contributes to oncogenic transformation...
  22. ncbi Proteasome inhibition induces glutathione synthesis and protects cells from oxidative stress: relevance to Parkinson disease
    Noriyuki Yamamoto
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46 29 Shimoadachi cho, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 282:4364-72. 2007
    ..These data suggest that proteasome inhibition afforded cytoprotection against oxidative stress by the elevation of glutathione content, and its elevation was mediated by p38 MAPK phosphorylation...
  23. pmc Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes
    D A Matthews
    Agouron Pharmaceuticals, Inc, 3565 General Atomics Court, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 96:11000-7. 1999
    ..Recently, one compound in this series, AG7088, has entered clinical trials...
  24. ncbi Multifunctional role of plant cysteine proteinases
    Małgorzata Grudkowska
    Plant Physiology and Biochemistry Department, Plant Breeding and Acclimatization Institute, Radzikow, Warsaw, Poland
    Acta Biochim Pol 51:609-24. 2004
    ..In this review an attempt was undertaken to illustrate these multiple roles of cysteine proteinases and the mechanisms underlying their action...
  25. ncbi Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis
    Alessio Nencioni
    Massachusetts Institute of Technology, Department of Biology, Center for Cancer Research, Cambridge, MA, USA
    Blood 105:3255-62. 2005
    ..Pharmacologic or genetic approaches targeting Mcl-1, including therapeutic RNAi, may increase the effectiveness of these compounds...
  26. ncbi Inhibition of human caspases by peptide-based and macromolecular inhibitors
    M Garcia-Calvo
    Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 273:32608-13. 1998
  27. pmc Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway
    A Mathew
    Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA
    Mol Cell Biol 18:5091-8. 1998
  28. ncbi Cysteine protease inhibitors as chemotherapy for parasitic infections
    J H McKerrow
    Department of Pathology, VA Medical Center, University of California, San Francisco 94121, USA
    Bioorg Med Chem 7:639-44. 1999
    ..This suggests that cysteine protease inhibitors may provide an alternative to traditional therapy in drug-resistant organisms...
  29. pmc Mutations in reovirus outer-capsid protein sigma3 selected during persistent infections of L cells confer resistance to protease inhibitor E64
    G S Baer
    Department of Microbiology and Immunology, and Elizabeth B Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Virol 71:4921-8. 1997
  30. ncbi Caspase inhibitors
    P G Ekert
    The Walter and Eliza Hall Institute of Medical Research, c o Post Office Royal Melbourne Hospital, Victoria 3050, Australia
    Cell Death Differ 6:1081-6. 1999
  31. pmc Plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development
    Ying Pei
    Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA
    Cell Microbiol 15:1508-26. 2013
    ..These data show that ICP may be important in regulating proteolytic processes during blood-stage development, and is likely playing a role in liver stage-hepatocyte interactions at the time of exoerythrocytic merozoite release. ..
  32. ncbi Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis
    R U Jänicke
    Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Dr, Singapore 117609, Republic of Singapore
    J Biol Chem 273:15540-5. 1998
  33. pmc Identification and characterization of a Drosophila proteasome regulatory network
    Josefin Lundgren
    Department of Molecular Biology and Functional Genomics, Stockholm University, S 106 91 Stockholm, Sweden
    Mol Cell Biol 25:4662-75. 2005
    ..Transfer of the 5' UTR from the proteasome subunit Rpn1/S2 to a noninducible promoter was sufficient to confer transcriptional upregulation of the reporter mRNA after proteasome inhibition...
  34. ncbi Human cystatin C forms an inactive dimer during intracellular trafficking in transfected CHO cells
    G S Merz
    New York State Office of Mental Retardation and Developmental Disabilities, Staten Island, New York, NY 10314, USA
    J Cell Physiol 173:423-32. 1997
    ..Similarly, its uptake by the cell also leads to its redimerization in the lysosomal pathway...
  35. ncbi Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression
    A Eggert
    Division of Oncology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA
    Cancer Res 61:1314-9. 2001
    ..Because many cytotoxic drugs induce caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might be an important mechanism of resistance to chemotherapy in NB...
  36. pmc The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis
    J Delic
    Laboratoire de Recherche Correspondant No2 du CEA DSV DRR, Fontenay Aux Roses Institut Curie, Paris, France
    Br J Cancer 77:1103-7. 1998
  37. pmc Exoerythrocytic Plasmodium parasites secrete a cysteine protease inhibitor involved in sporozoite invasion and capable of blocking cell death of host hepatocytes
    Annika Rennenberg
    Bernhard Nocht Institute for Tropical Medicine, Department of Molecular Parasitology, Hamburg, Germany
    PLoS Pathog 6:e1000825. 2010
  38. ncbi Evidence that a rapidly turning over protein, normally degraded by proteasomes, regulates hsp72 gene transcription in HepG2 cells
    M Zhou
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 271:24769-75. 1996
    ..Overall, our results suggest that a rapidly turning over protein that is normally degraded by proteasomes may be involved in the regulation of Hsp70 synthesis via effects on the hsp70 transcriptional factor, HSF1...
  39. ncbi Inhibition of programmed cell death impairs in vitro vascular-like structure formation and reduces in vivo angiogenesis
    Inmaculada Segura
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Campus de Cantoblanco, E 28049 Madrid, Spain
    FASEB J 16:833-41. 2002
    ..This evidence indicates that endothelial cell apoptosis may be relevant for precise vascular tissue rearrangement in in vitro and in vivo angiogenesis...
  40. ncbi Falcipains, Plasmodium falciparum cysteine proteases as key drug targets against malaria
    C Teixeira
    Centro de Investigação em Química da Universidade do Porto, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, R Campo Alegre, 687, P 4169 007 Porto, Portugal
    Curr Med Chem 18:1555-72. 2011
  41. pmc Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella
    Marie Schaeffer
    Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow, Scotland, United Kingdom
    Antimicrob Agents Chemother 56:1190-201. 2012
    ..The oxazolone scaffold is a novel cysteine peptidase inhibitor; it may thus find widespread use...
  42. ncbi Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages
    L Verdot
    Laboratoire d Enzymologie et de Chimie des Protéines, Universite Francois Rabelais, F37032 Tours, France
    J Biol Chem 271:28077-81. 1996
    ..demonstrate that members of all 3 cystatin families share another common property unrelated to their function of cysteine proteinase inhibitors, i.e. up-regulation of NO production, which biological significance remains to be elucidated.
  43. ncbi FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex
    M Muzio
    University of Michigan Medical School Department of Pathology, Ann Arbor, Michigan 48109, USA
    Cell 85:817-27. 1996
    ..Taken together, this is unique biochemical evidence to link a death receptor physically to the proapoptotic proteases of the ICE/CED-3 family...
  44. ncbi Cruzain : the path from target validation to the clinic
    Mohammed Sajid
    Afd Parasitologie, Leiden University Medical Center, Leiden, The Netherlands
    Adv Exp Med Biol 712:100-15. 2011
  45. ncbi Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain
    Changlian Zhu
    Perinatal Center, Department of Physiology, Goteborg University, Goteborg, Sweden
    J Neurochem 86:306-17. 2003
    ..In summary, AIF-mediated cell death may be an important mechanism of HI-induced neuronal loss in the immature brain...
  46. pmc Inhibition of Plasmodium falciparum oocyst production by membrane-permeant cysteine protease inhibitor E64d
    S Eksi
    Department of Biology, Loyola University Chicago, 6525 N Sheridan Rd, Chicago, IL 60626, USA
    Antimicrob Agents Chemother 51:1064-70. 2007
    ..The ability of a membrane-permeant cysteine protease inhibitor to significantly reduce malaria parasite transmission suggests that future drug design should include evaluation of gametogenesis and sporogonic development...
  47. ncbi Expression, purification, and inhibitory activities of mouse cytotoxic T-lymphocyte antigen-2alpha
    Mitsuhiro Kurata
    Laboratory of Biochemistry and Radiation Biology, Department of Veterinary Sciences, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753 8515, Japan
    Protein Expr Purif 32:119-25. 2003
    ..Our results indicate that mouse CTLA-2alpha is a selective inhibitor of the cathepsin L-like cysteine proteinases...
  48. ncbi Peptidomimetic inhibitors of cathepsin K
    W Cameron Black
    Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Que, Canada
    Curr Top Med Chem 10:745-51. 2010
    ..Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis...
  49. pmc Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L
    T Bevec
    Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia
    J Exp Med 183:1331-8. 1996
    ..The Ii inhibitory fragment shows no sequence homology with the known cysteine protease inhibitors, and may, therefore, represent a new class...
  50. ncbi Bombyx cysteine proteinase inhibitor (BCPI) homologous to propeptide regions of cysteine proteinases is a strong, selective inhibitor of cathepsin L-like cysteine proteinases
    M Kurata
    Laboratory of Biochemistry and Radiation Biology, Department of Veterinary Sciences, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan
    J Biochem 130:857-63. 2001
    ..Recombinant BCPI lacking the two C-terminal amino acid residues still retained substantial inhibitory activity. Our results indicate that BCPI is a stable and highly selective inhibitor of cathepsin L-like cysteine proteinases...
  51. ncbi Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury
    Susan M Knoblach
    Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA
    J Cereb Blood Flow Metab 24:1119-32. 2004
    ..These data suggest that neuroprotection by z-DEVD-fmk may, in part, reflect inhibition of calpain-related necrotic cell death...
  52. ncbi Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis
    H Fauvel
    , Lille Cedex, 59045, France
    Am J Physiol Heart Circ Physiol 280:H1608-14. 2001
    ..Caspase inhibition strategy may represent a therapeutic approach to endotoxin-induced myocardial dysfunction...
  53. ncbi Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding
    G D Lin
    Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294, USA
    Nat Struct Biol 4:539-47. 1997
    ..The crystal structure of a Ca2+ bound domain VI-inhibitor (PD150606) complex has been refined to 2.1 A resolution. A possible mode for calpain inhibition is discussed...
  54. ncbi Synthesis and biological evaluation of reversible inhibitors of IdeS, a bacterial cysteine protease and virulence determinant
    Kristina Berggren
    Department of Chemistry, Medicinal Chemistry, University of Gothenburg, Goteborg, Sweden
    Bioorg Med Chem 17:3463-70. 2009
    ..Eight compounds were identified as inhibitors of IdeS in an in vitro assay. The most potent compounds contained an aldehyde function, thus acting as efficient reversible inhibitors, nitrile and azide derivatives showed moderate activity...
  55. ncbi Expression of type 2 cystatin genes CST1-CST5 in adult human tissues and the developing submandibular gland
    D P Dickinson
    Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, Georgia 30912 1124, USA
    DNA Cell Biol 21:47-65. 2002
  56. ncbi Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis
    Delphine Milhas
    INSERM U466, Institut Louis Bugnard, Toulouse, France
    J Biol Chem 280:19836-42. 2005
    ..Altogether, our data strongly suggest that caspase-10 can serve as an initiator caspase in Fas signaling leading to Bid processing, caspase cascade activation, and apoptosis...
  57. ncbi Successful therapy of lethal murine visceral leishmaniasis with cystatin involves up-regulation of nitric oxide and a favorable T cell response
    L Das
    Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India
    J Immunol 166:4020-8. 2001
    ..These studies provide a promising alternative for protection against leishmaniasis with a switch of CD4(+) differentiation from Th2 to Th1, indicative of long-term resistance...
  58. pmc Proteasomal inhibition enhances glucocorticoid receptor transactivation and alters its subnuclear trafficking
    Bonnie J Deroo
    Chromatin and Gene Expression Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Cell Biol 22:4113-23. 2002
    ..Proteasomes may therefore impact steroid receptor action at multiple levels and exert distinct effects on individual receptor types...
  59. ncbi Signaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: involvement of ERK1/2, NF-kappaB and JAK/STAT pathways
    Susanta Kar
    Infectious Diseases and Immunology Division, Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Kolkata, India
    Eur J Immunol 39:741-51. 2009
    ..Understanding the molecular mechanisms through which cystatin modulates macrophage effector responses will contribute to better define its potential for macrophage-associated diseases, in general...
  60. ncbi A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection
    Hulya Karatas
    Department of Neurology, Faculty of Medicine and Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey
    J Neurosci 29:13761-9. 2009
    ..Thus, chitosan nanospheres open new and exciting opportunities for brain delivery of biologically active peptides that are useful for the treatment of CNS disorders...
  61. ncbi Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells
    N P Dantuma
    Microbiology and Tumor Biology Center, Karolinska Institutet, S 171 77 Stockholm Sweden
    Nat Biotechnol 18:538-43. 2000
    ..These reporters provide a new powerful tool for elucidation of the ubiquitin/proteasome pathway and for high throughput screening of compounds that selectively modify proteolysis in vivo...
  62. ncbi Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha
    Thilo Hagen
    Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
    Science 302:1975-8. 2003
    ..Thus, the signaling consequences of hypoxia may be profoundly modified by nitric oxide...
  63. ncbi Both Rb and E7 are regulated by the ubiquitin proteasome pathway in HPV-containing cervical tumor cells
    J Wang
    Center for Molecular Biology of Oral Diseases, College of Dentistry (M/C 860, University of Illinois at Chicago, 60612, USA
    Oncogene 20:4740-9. 2001
    ..Taken together, this study suggests that targeted inhibition of Rb proteolysis will be required for restoring Rb function in HPV-containing cervical cancer cells...
  64. ncbi Caspase-dependent proteolysis of integral and peripheral proteins of nuclear membranes and nuclear pore complex proteins during apoptosis
    B Buendia
    Département de Biologie Supramoléculaire et Cellulaire, Institut Jacques Monod, CNRS, Universite Paris 7, Tour 43, 75251 Paris Cedex 05, France
    J Cell Sci 112:1743-53. 1999
  65. ncbi The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH
    Yong Hwan Han
    Department of Physiology, Medical School, Centers for Healthcare Technology Development, Institute for Medical Sciences Chonbuk National University, Jeonju, Korea
    Oncol Rep 22:215-21. 2009
    ..In conclusion, MG132 inhibited the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis. The changes of ROS and GSH by MG132 were closely related to apoptosis in HeLa cells...
  66. pmc Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells
    Peng Fei Ge
    1 Department of Neurosurgery, 1st Hospital of Jilin University, Changchun, Jilin 130021, China 2 Department of Neurosurgery, Xuanwu Hospital of Capital University of Medical Science, Beijing 100053, China
    Acta Pharmacol Sin 30:1046-52. 2009
    ..In this study, we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells...
  67. pmc Bax directly induces release of cytochrome c from isolated mitochondria
    J M Jurgensmeier
    Program on Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 95:4997-5002. 1998
  68. ncbi Cowpea bruchid Callosobruchus maculatus uses a three-component strategy to overcome a plant defensive cysteine protease inhibitor
    K Zhu-Salzman
    Department of Entomology, Texas A and M University, College Station, TX 77843, USA
    Insect Mol Biol 12:135-45. 2003
    ..Our results suggest that the cowpea bruchid adapts to the challenge of scN by qualitative and quantitative remodelling of its digestive protease complement, and by activating scN-degrading protease activity...
  69. ncbi Salivary (SD-type) cystatins: over one billion years in the making--but to what purpose?
    D P Dickinson
    Medical College of Georgia, School of Dentistry, Department of Oral Biology and Maxillofacial Pathology, 1120 15th Street, Augusta, GA 30912, USA
    Crit Rev Oral Biol Med 13:485-508. 2002
  70. ncbi The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
    Jacques Yves Gauthier
    Merck Frosst Centre for Therapeutic Research, 16711 Transcanada Hwy, Kirkland, Que, Canada
    Bioorg Med Chem Lett 18:923-8. 2008
    ..Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors...
  71. ncbi A novel inhibitor protein for Bombyx cysteine proteinase is homologous to propeptide regions of cysteine proteinases
    Y Yamamoto
    Department of Biochemistry and Radiation Biology, College of Agriculture, Yamaguchi University, Japan
    FEBS Lett 448:257-60. 1999
    ..The results suggest that some cysteine proteinase proregions may have evolved as autonomous modules and become inhibitor proteins for cysteine proteinases...
  72. pmc Mitochondrial release of caspase-2 and -9 during the apoptotic process
    S A Susin
    Centre National de la Recherche Scientifique, UPR 420, F 94801 Villejuif, France
    J Exp Med 189:381-94. 1999
  73. ncbi Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease
    T W Kim
    Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Science 277:373-6. 1997
  74. pmc Falstatin, a cysteine protease inhibitor of Plasmodium falciparum, facilitates erythrocyte invasion
    Kailash C Pandey
    Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA
    PLoS Pathog 2:e117. 2006
    ..This mechanism of regulation of proteolysis suggests new strategies for the development of antimalarial agents that specifically disrupt erythrocyte invasion...
  75. ncbi Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi
    A C Monteiro
    , Bloco G, CCS, Universidade Federal do Rio de Janeiro, , Rio de Janeiro, CEP 21990-400, Brazil
    J Cell Sci 114:3933-42. 2001
    ..The intersection of chagasin and cruzipain trafficking pathways may represent a checkpoint for downstream regulation of proteolysis in trypanosomatid protozoa...
  76. ncbi Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events
    R Mancini
    Department of Molecular Pathology and Medicine, DIBIT San Raffaele Scientific Institute, 20132 Milan, Italy
    FASEB J 14:769-78. 2000
    ..Taken together, these results suggest that active proteasomes are required for the extraction of Ig subunits from the ER, though the requirements for retrotranslocation may differ among individual substrates...
  77. pmc Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson's disease
    Anthony C Vernon
    Department of Neuroscience, Kings College London, The James Black Centre, UK
    BMC Neurosci 11:1. 2010
    ..Therefore, in this study we have utilised MRI to scan in vivo brains from rodents bearing a nigrostriatal lesion induced by intranigral injection of the proteasome inhibitor lactacystin...
  78. ncbi Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review)
    J Kos
    Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, 1000 Ljubljana, Slovenia
    Oncol Rep 5:1349-61. 1998
    ..Their application for diagnosis, follow-up and the anticancer therapy has also been proposed...
  79. ncbi Transfection of mGSTA4 in HL-60 cells protects against 4-hydroxynonenal-induced apoptosis by inhibiting JNK-mediated signaling
    J Z Cheng
    Department of Human Biological Chemistry and Genetics, UTMB, Galveston, Texas 77555-1067, USA
    Arch Biochem Biophys 392:197-207. 2001
    ..These results show that 4-HNE mediates apoptosis through its effects on JNK and caspase 3, and that 4-HNE metabolizing GST isozyme(s) may be important in the regulation of this pathway of oxidative-stress-induced apoptosis...
  80. ncbi Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients
    Aleksandar Rakovic
    Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, 23562 Lübeck, Germany
    Hum Mol Genet 19:3124-37. 2010
  81. pmc Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model
    Samuel G Melendez-Lopez
    Department of Pathology, University of California, San Diego, San Diego, California 92103 8416, USA
    Eukaryot Cell 6:1130-6. 2007
    ..role of secreted cysteine proteinases in amebic invasion, we tested the effect of the vinyl sulfone cysteine proteinase inhibitors K11777 and WRR483 on invasion of human colonic xenografts...
  82. ncbi Role of cysteine proteinase inhibitors in preference of Japanese beetles (Popillia japonica) for soybean (Glycine max) leaves of different ages and grown under elevated CO2
    Jorge A Zavala
    Institute for Genomic Biology, University of Illinois, Urbana Champaign, IL, USA
    Oecologia 161:35-41. 2009
    ..hormones jasmonic acid and ethylene; these in turn decrease the gene expression and activity of cysteine proteinase inhibitors (CystPIs), the principal antiherbivore defenses in foliage...
  83. ncbi Over-expression of calpastatin inhibits calpain activation and attenuates myocardial dysfunction during endotoxaemia
    Xiaoping Li
    Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
    Cardiovasc Res 83:72-9. 2009
    ..The present study was to investigate the roles of calpain/calpastatin system in cardiomyocyte caspase-3 activation, TNF-alpha expression, and myocardial dysfunction during LPS stimulation...
  84. pmc Characterization of Solanum tuberosum multicystatin and its structural comparison with other cystatins
    Mark S Nissen
    School of Molecular Biosciences, Washington State University, Pullman, Washington 99164 4660, USA
    Plant Cell 21:861-75. 2009
    ..The unique molecular properties of the oligomeric PMC crystal are discussed in relation to its potential function in regulating the activity of proteases in potato tubers...
  85. ncbi Immunomodulatory properties of cystatins
    B Vray
    Laboratoire d Immunologie Expérimentale, Faculte de Medecine, Universite Libre de Bruxelles, Brussels, Belgium
    Cell Mol Life Sci 59:1503-12. 2002
    ..On the whole, cystatins and cystatin-like molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of this property, leading to practical applications in immunotherapy...
  86. ncbi Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
    D W Nicholson
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
    Nature 376:37-43. 1995
    ..A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death...
  87. ncbi Regulation of p53 stability by Mdm2
    M H Kubbutat
    ABL Basic Research Program, NCI FCRDC, Frederick, Maryland 21702 1201, USA
    Nature 387:299-303. 1997
    ..Furthermore, mechanisms regulating the Mdm2-induced degradation of p53 may play a role in controlling the extent and duration of the p53 response...
  88. ncbi Cystatin C
    David J Newman
    South West Thames Institute for Renal Research, St Helier Hospital, Carshalton, Surrey, UK
    Ann Clin Biochem 39:89-104. 2002
  89. ncbi Conversion of Bcl-2 to a Bax-like death effector by caspases
    E H Cheng
    Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA
    Science 278:1966-8. 1997
    ..Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus-induced apoptosis. Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death...
  90. ncbi Survivin expression in human osteosarcoma is a marker for survival
    K Trieb
    Department of Orthopedics, University of Colorado Health Sciences Center, Denver
    Eur J Surg Oncol 29:379-82. 2003
    ..Survivin is a member of the inhibitor of apoptosis (IAP) protein gene family and is expressed both during normal fetal development and in human cancer...
  91. pmc Prevention of lymphocyte cell death in sepsis improves survival in mice
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:14541-6. 1999
    ..Caspase inhibitors may represent a treatment strategy in this highly lethal disorder...
  92. ncbi The cysteine protease activity of Colorado potato beetle (Leptinotarsa decemlineata Say) guts, which is insensitive to potato protease inhibitors, is inhibited by thyroglobulin type-1 domain inhibitors
    K Gruden
    Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia
    Insect Biochem Mol Biol 28:549-60. 1998
    ..This demonstrated the potential of equistatin to protect crops from insect attack...
  93. ncbi C-Terminal extension of a plant cysteine protease modulates proteolytic activity through a partial inhibitory mechanism
    Sruti Dutta
    Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India
    FEBS J 278:3012-24. 2011
    ..These data suggest that the CT-extension has an inhibitory role in the proteolytic activity of ervatamin-C but does not have a major role either in stabilizing the enzyme or in its folding mechanism...
  94. ncbi Tigutcystatin, a cysteine protease inhibitor from Triatoma infestans midgut expressed in response to Trypanosoma cruzi
    Diego S Buarque
    Department of Biochemistry, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, 04044 020 Sao Paulo, SP, Brazil
    Biochem Biophys Res Commun 413:241-7. 2011
    ..cruzi. Together, these results indicate that Tigutcystatin may be involved in modulation of T. cruzi in intestinal tract by inhibiting parasite cysteine proteases, which represent the virulence factors of this protozoan...
  95. pmc α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB
    Koen Steert
    Department of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
    ChemMedChem 5:1734-48. 2010
    ..8; however, in vitro whole-organism screening against a panel of protozoan parasites did not fully correlate with the observed inhibition of the cysteine protease...
  96. pmc The role of cysteine proteinases and their inhibitors in the host-pathogen cross talk
    Natasa Kopitar-Jerala
    Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
    Curr Protein Pept Sci 13:767-75. 2012
    ..In this review, I provide an update on the most recent developments regarding the role of proteinases and their inhibitors in the initiation and regulation of immune responses...
  97. ncbi The specificity of trichomonad cysteine proteinases analysed using fluorogenic substrates and specific inhibitors
    M J North
    Department of Biological and Molecular Sciences, School of Natural Sciences, University of Stirling, U K
    Mol Biochem Parasitol 39:183-93. 1990
    ..vaginalis and T. foetus. The information on the specificities will be useful for assessing the features required in proteinase inhibitors if they are to be of potential value as antitrichomonal agents...
  98. ncbi Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness
    S Sugawara
    Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai, Japan
    J Immunol 165:411-8. 2000
    ..These results suggest that gingipains preferentially cleave monocyte CD14, resulting in attenuation of the cellular recognition of bacteria, and as a consequence sustain chronic inflammation...
  99. ncbi Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung
    Mizuki Ikehara
    Department of Thoracic Oncology, Kanagawa Cancer Center, Asahi ku, Yokohama 241 0815, Japan
    Oncol Rep 9:835-8. 2002
    ..014; Wilcoxon test, p=0.021). It can be concluded that the expression of survivin in tumor cells is a factor of poor prognosis in patients with small adenocarcinoma of the lung...
  100. ncbi Orally bioavailable cathepsin K inhibitors with pyrrolopyrimidine scaffold
    Naoki Teno
    Novartis Institutes for BioMedical Research, Tsukuba, Ibaraki, Japan
    Curr Top Med Chem 10:752-66. 2010
    ..This article constitutes a near comprehensive review of the published scientific literature on small molecule non-peptidic inhibitors for cathepsin K developed by Novartis...
  101. pmc Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
    Dusan Kordis
    Department of Biochemistry and Molecular and Structural Biology, J, Stefan Institute, Ljubljana, Slovenia
    BMC Evol Biol 9:266. 2009
    ..Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea...

Research Grants70

    Sharon Reed; Fiscal Year: 2001
    ..of cystine proteinases and their role in peptide degradation and evaluating the effect of specific cysteine proteinase inhibitors on parasite survival and identify their site of action...
    James Cox; Fiscal Year: 2001
    ..The overall goal of this project is to elucidate steps by which natural cysteine proteinase inhibitors, the cystatins, may act as antimetastatic agents...
    DANIEL RICH; Fiscal Year: 1992
    ..Develop a 3- dimensional model for the human cysteine proteinases, cathepsin B, H, and L, for which X-ray crystal structures are not available...
    Gurrinder Bedi; Fiscal Year: 1990
    b>Cysteine proteinase inhibitors of the cystatin superfamily are grouped into three families on the basis of their molecular structure...
    Brian Liu; Fiscal Year: 1993
    ..In this proposal, we will determine the effects of cysteine proteinase inhibitors in inhibiting the activity of plasma membrane bound cathepsin B at a biochemical level using enzyme ..
    Douglas Dickinson; Fiscal Year: 1991
    ..The type 2 cystatins are a group of cysteine proteinase inhibitors that are major protein constituents of saliva...
    Bonnie Sloane; Fiscal Year: 1992 to determine the role(s) of cysteine proteinases (in particular cathepsin B) and endogenous low Mr cysteine proteinase inhibitors (CPI) in tumor cell metastasis. Increases activities of several cysteine proteinases, e.g...
  8. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2007
    ..abstract_text> ..
  9. Targeting Cysteine Proteases: Antiparasitic Chemotherapy
    James McKerrow; Fiscal Year: 2008
    ..No Abstract Provided. ..
  10. Clinical & Molecular Studies of Drug Resistant Malaria
    Philip Rosenthal; Fiscal Year: 2008
    ..abstract_text> ..
  11. Water-Soluble and Metabolically Stable Calpain Inhibitors as Cardioprotectants
    ISAAC DONKOR; Fiscal Year: 2008
    ..Furthermore, the proposed studies will provide mechanistic insight into the mode of action of calpain inhibitors as cardioprotectants. ..
  12. High Throughput Assay for Screening Compounds(RMI)
    James McKerrow; Fiscal Year: 2005
    ..Computational and informatics capability is in place to acquire, store and cross-reference this data, and provide access to the scientific community through an open-source website. ..
  13. Chemoprevention Potential of Calpain Inhibitors
    ISAAC DONKOR; Fiscal Year: 2007
    ..The proposal is significant and innovative because it seeks to investigate calpain as a pharmacological target for the discovery of a new class of chemoprevention agents. [unreadable] [unreadable] [unreadable]..
  14. Targeting Calpain for Novel Anticancer Agents
    ISAAC DONKOR; Fiscal Year: 2005
    ..Additionally, the compounds are useful biomedical tools for investigating the intracellular roles of Calpain due to their metabolic stability. The compounds are also potential anticancer agents. ..
  15. Falcipain Cysteine Proteases of Malaria Parasites
    Philip Rosenthal; Fiscal Year: 2005
    ..Experiments designed to accomplish these aims should improve our understanding of the biology of malaria parasites and aid in the characterization of falcipains as potential drug targets. ..
  16. Resistance of Malaria Parasites to Artemisinin-Based Combination Therapies
    Philip Rosenthal; Fiscal Year: 2008
    ..abstract_text> ..
    KEVIN MCNAUGHT; Fiscal Year: 2008
    ..These studies will test our hypothesis that inadequate proteasomal function underlies both vulnerability and degeneration of the SNc in sporadic Parkinson's disease. ..
    ISAAC DONKOR; Fiscal Year: 2002
    ..Selected potent and cell permeable inhibitors will be tested in the rat isolated heart ischemia model for cardioprotective effect. ..
    Philip Rosenthal; Fiscal Year: 2003
    ..This evaluation is also likely to identify specific falcipain inhibitors with potent antimalarial activity that will be ready for initial testing against human malaria. ..
    RICHARD POLLENZ; Fiscal Year: 2005
    ..abstract_text> ..
  21. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..Serpin regulation of opioid peptides that mediate analgesia and stress may lead to development of new therapeutic approaches in pain and neurologic disease. ..
  22. Beta-Secretase Assays to Discover Drugs for Alzheimer's
    Gregory Hook; Fiscal Year: 2004
    ..ActiveSite Biotech is in a position to exclusively sell, license, or partner lead drug inhibitors resulting from the Phase II study. ..
    Vivian Hook; Fiscal Year: 2009
    ..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
  24. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian Hook; Fiscal Year: 2004
    ..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
  25. Inhibitors of beta-Amyloid Production in Alzheimer's
    Gregory Hook; Fiscal Year: 2007
    ..Specifically, we will assess the affects of these peptidomimetics on beta-amyloid secretion in primary neuronal cultures and in vivo. ..
  26. POMC Processing and Beta-Endorphine-Related Opioid Peptides
    Vivian Y H Hook; Fiscal Year: 2010
    ..New findings from this project will enhance our knowledge of the complexity of biosynthetic mechanisms for endogenous opioid and neuropeptide systems. ..
  27. Gamma Secretase Assays to Discover Drugs for Alzheimer's
    Gregory Hook; Fiscal Year: 2006
    ..Results will likely identify novel lead compounds for future pre-clinical animal studies for development of effective drugs for AD. ..
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
    RICHARD POLLENZ; Fiscal Year: 2008
    ..e. steroid hormone receptors). [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  30. The Role of MicroRNA in Hepatocarcinogenesis
    Kalpana Ghoshal; Fiscal Year: 2007
    ..Further, this proposal fits well with the mission/goals set forth by multiple institutes that include NCI, NIDDK and NIAAA n the etiology, prevention and treatment of hepatocellular carcinomas. [unreadable] [unreadable] [unreadable]..
  31. Proteasome function in the aging retina
    Deborah A Ferrington; Fiscal Year: 2010
    ..Results from these experiments will help verify that immunoproteasome is an essential component of the retinal stress response and plays a fundamental role in maintaining retinal health. ..
  32. Safety of Lung Delivered Tissue Plasminogen Activator
    KATHLEEN STRINGER; Fiscal Year: 2006
    ..The proposed Phase II project will complement and extend our Phase I work and will facilitate the development of a promising new, greatly needed therapeutic for the treatment of ARDS. ..
  33. High Resolution Hybrid FT-ICR Mass Spectrometer
    Joseph Loo; Fiscal Year: 2006
    ..The instrument will be a centerpiece and will be supported and administered by the newly-created Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution. [unreadable] [unreadable] [unreadable]..
    Jeffrey Kordower; Fiscal Year: 2006
    ..This application will determine whether potent dopaminergic gene therapies influence dyskinesias in the best animal model of PD. ..
    Pothana Saikumar; Fiscal Year: 2007
    ..In vivo gene silencing of Bax will be attempted in efforts to block up regulation of Bax and thereby prevent cell injury in the ischemic kidney. ..
  36. Role of Survivin in Blood Stem Cell Cycle and Apoptosis
    LOUIS PELUS; Fiscal Year: 2007
  37. Macromolecular Therapy for Improved Treatment of Rheumatoid Arthritis
    Dong Wang; Fiscal Year: 2009
    ..Eventually, this novel delivery system would lead to improved efficacy and safety profiles for treatment of rheumatoid arthritis and other inflammatory joint disorders. ..
  38. Reconstitution of Protective CMV Immunity and Immune Regulation After HAART
    Adriana Weinberg; Fiscal Year: 2008
    ..These analyses will define the role of TREG in the inadequate CMV immune reconstitution of HAART recipients. [unreadable] [unreadable] [unreadable] [unreadable]..
  39. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
    ..Dudley Strickland. ..
  40. Center for Nutrient-Gene Interaction in Cancer Preventi*
    Stephen Barnes; Fiscal Year: 2008
    ..In addition to the main projects, the Center will organize a competitive Pilot Project/Developmental program for the evaluation of new ideas and methods pertinent to the overall development of the Center. ..
  41. TH and GTPCHI gene therapy for Parkinson's disease
    Jeffrey H Kordower; Fiscal Year: 2010
    ..These studies will determine the safety and efficacy of gene delivery of LDOPA and determine whether this approach is appropriate for clinical trials. ..
  42. MAPK/PKR Modulation of Diaphragm Weakness
    Gerald S Supinski; Fiscal Year: 2010
    ..We will both characterize the effects of inflammation on DISC formation, localization, and autocatalytic activity and determine if these alterations can be blocked by inhibition of p38, JNK, and/or PKR signaling pathways. ..
  43. Hollings Cancer Center Planning Grant
    Andrew Kraft; Fiscal Year: 2005
    ..abstract_text> ..
    Mark Segal; Fiscal Year: 2003
  45. Sex in Viral Myocarditis
    Sally Huber; Fiscal Year: 2004
    ..These studies may provide new insights as to how viruses affect developing host defense responses and how hormones can modulate this initial response. ..
  46. Conference on Photodynamic Therapy
    David Kessel; Fiscal Year: 2002
    ..The most recent PDT meeting, sponsored by the International Photodynamic Assn, has more than 600 participants. ..
    Mathieu Lesort; Fiscal Year: 2004
  48. Cathepsin B in Progression of Prostatic Lesion to Cancer
    AKHOURI SINHA; Fiscal Year: 2004
    Muxiang Zhou; Fiscal Year: 2004
    John Crabb; Fiscal Year: 2002
    ..The proposed studies will lead to a better understanding of the structure, function and regulation of CRALBP and the visual disorders with which at may be associated. ..
  51. Novel Signaling Targets in GI Neuroendocrine Tumors
    Herbert Chen; Fiscal Year: 2005
    ..The possibility that raf-l-mediated hormone suppression could be induced by a soluble factor would provide a plausible, therapeutic delivery method. ..
    John Anagli; Fiscal Year: 2005
    ..This project can provide a foundation at the molecular level for rational development of therapeutic agents to modulate PAI-1 activity. ..
  53. Suppression of Breakthrough Bleeding in LNG-IUS Users
    Ov Slayden; Fiscal Year: 2006
    ..The proposal brings basic scientists and clinicians together for a "bench to bedside" approach that will advance women's health and improve contraceptive technology. ..
  54. Retinal Cell Death in Diabetic Retinopathy
    Susanne Mohr; Fiscal Year: 2006
    ..abstract_text> ..
  55. Calcium-activated protease in cataract formation
    Thomas Shearer; Fiscal Year: 2006
    ..unreadable] [unreadable] 3. Define the roles of calpain 10 in human lens. [unreadable] [unreadable] These studies will provide a rational basis for the use of protease inhibitors to prevent cataracts. ..
    LINDA MUSIL; Fiscal Year: 2004
    ..These studies will elucidate the causes of phenotypic diversity in CMTX as well as provide the first molecular insights into the quality control mechanisms that govern the fidelity of connexin assembly into gap junctional channels. ..
  57. Tenth International Congress on Ceroid Lipofuscinoses
    Glyn Dawson; Fiscal Year: 2005
  58. 9.4 Tesla Fourier Transform Mass Spectrometer
    Stephen Barnes; Fiscal Year: 2002
    ..Overall, the FT-MS instrument will sustain the high quality of biomedical research that is a hallmark of UAB. ..
  59. CDI and Gamma Delta+ in Viral Myocarditis
    Sally Huber; Fiscal Year: 2005
    ..abstract_text> ..
    Arnab Chakravarti; Fiscal Year: 2003
    ..Specific Aim number 3: To determine whether the deregulation of E2F dependent transcription is correlated with the tumorigenic potential of RB -/- cells in-vivo. ..
  61. 25-hydroxy-D3 as a possible chemopreventive agent for breast cancer
    Xinjian Peng; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    Melanie Mediavilla Varela; Fiscal Year: 2008
    ..These studies will provide insights into the mechanisms underlying prostate tumor resistance to cell death and lead to development of novel therapeutic strategies for PCa. [unreadable] [unreadable] [unreadable]..
  63. Caspase Mediated Diaphragmatic Dysfunction
    GERALD SUPINSKI; Fiscal Year: 2009
    ..These experiments will use both transgenic animal models and C2C12 cells to assess the effect of genetic and chemical inhibition of superoxide/nitric oxide on caspase responses. ..
  64. Divalent Metal Transporter: Role in Manganese Toxicity
    JEROME ROTH; Fiscal Year: 2004
  65. Anti-Leukemic Activity of the Novel Triterpeniod CDDO
    Michael Andreeff; Fiscal Year: 2004
    ..The long-term goal of our proposed mechanistic and efficacy studies is to determine the potential of CDDO as a novel anti-leukemia and anti-tumor agent. ..
    GERALD SUPINSKI; Fiscal Year: 2001
    ..These data suggest that the proposed experiments should provide important information regarding the pathogenesis of sepsis-induced muscle dysfunction. ..
  67. A sensitive triple quadrupole mass spectrometer
    Stephen Barnes; Fiscal Year: 2004
    ..It is anticipated that a commercial nanospray interface for use in nanoLC-MS analysis will be available by the fall of 2003. ..
    Piotr Zimniak; Fiscal Year: 2005
    ..The proposed work is intended to advance the understanding of the physiological and toxicological consequences of oxidative stress, as mediated by 4-HNE. ..
    JAMES MC CUBREY; Fiscal Year: 2001
    ..An understanding of how these signal transduction and apoptotic pathways impinge upon one another will further our comprehension of the consequences of abnormal oncogene activation and tumor progression. ..