R Siman

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerability
    R Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 20:8717-26. 2000
  2. ncbi request reprint Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation
    R Siman
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:44736-43. 2001
  3. ncbi request reprint Novel surrogate markers for acute brain damage: cerebrospinal fluid levels corrrelate with severity of ischemic neurodegeneration in the rat
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Cereb Blood Flow Metab 25:1433-44. 2005
  4. ncbi request reprint Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brain
    R Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    Neuroscience 129:615-28. 2004
  5. ncbi request reprint Proteins released from degenerating neurons are surrogate markers for acute brain damage
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Neurobiol Dis 16:311-20. 2004
  6. ncbi request reprint Localization of presenilin-nicastrin complexes and gamma-secretase activity to the trans-Golgi network
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, JMB162, Philadelphia, PA 19104 6084, USA
    J Neurochem 84:1143-53. 2003
  7. ncbi request reprint Calpain activity in the rat brain after transient forebrain ischemia
    R W Neumar
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA
    Exp Neurol 170:27-35. 2001
  8. ncbi request reprint Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition
    Michael N DeRidder
    Department of Bioengineering, University of Pennsylvania, 3320 Smith Walk, Room 105E, Hayden Hall, Philadelphia, PA 19104, USA
    Neurobiol Dis 22:165-76. 2006
  9. pmc Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma
    Xiao Han Chen
    Department of Neurosurgery, University of Pennsylvania, 105C Hayden Hall, 3320 SmithWalk, Philadelphia, PA 19104 6316, USA
    Am J Pathol 165:357-71. 2004
  10. ncbi request reprint Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation
    Zhaoming Chen
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104 4283, USA
    Neurosci Lett 376:166-70. 2005

Research Grants

  1. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2007

Collaborators

Detail Information

Publications26

  1. ncbi request reprint Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerability
    R Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 20:8717-26. 2000
    ..Instead, enhanced amyloidogenic processing of APP likely is critical to the pathogenesis of PS-1-linked FAD...
  2. ncbi request reprint Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation
    R Siman
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:44736-43. 2001
    ....
  3. ncbi request reprint Novel surrogate markers for acute brain damage: cerebrospinal fluid levels corrrelate with severity of ischemic neurodegeneration in the rat
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Cereb Blood Flow Metab 25:1433-44. 2005
    ..Measurement of 14-3-3beta and calpain-cleaved tau may be useful for the minimally invasive diagnosis, prognosis, and therapeutic evaluation of acute brain damage...
  4. ncbi request reprint Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brain
    R Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    Neuroscience 129:615-28. 2004
    ..The subcellular localization of gamma-secretase subunits is consistent with a nerve terminal source for amyloid aggregates...
  5. ncbi request reprint Proteins released from degenerating neurons are surrogate markers for acute brain damage
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Neurobiol Dis 16:311-20. 2004
    ....
  6. ncbi request reprint Localization of presenilin-nicastrin complexes and gamma-secretase activity to the trans-Golgi network
    Robert Siman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, JMB162, Philadelphia, PA 19104 6084, USA
    J Neurochem 84:1143-53. 2003
    ..The findings provide further evidence that presenilin-containing complexes are the gamma-secretase, and indicate that presenilins also regulate gamma-secretase assembly...
  7. ncbi request reprint Calpain activity in the rat brain after transient forebrain ischemia
    R W Neumar
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA
    Exp Neurol 170:27-35. 2001
    ....
  8. ncbi request reprint Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition
    Michael N DeRidder
    Department of Bioengineering, University of Pennsylvania, 3320 Smith Walk, Room 105E, Hayden Hall, Philadelphia, PA 19104, USA
    Neurobiol Dis 22:165-76. 2006
    ....
  9. pmc Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma
    Xiao Han Chen
    Department of Neurosurgery, University of Pennsylvania, 105C Hayden Hall, 3320 SmithWalk, Philadelphia, PA 19104 6316, USA
    Am J Pathol 165:357-71. 2004
    ..The abnormal concentration of these factors may lead to APP proteolysis and Abeta formation within the axonal membrane compartment...
  10. ncbi request reprint Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation
    Zhaoming Chen
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104 4283, USA
    Neurosci Lett 376:166-70. 2005
    ..These results indicate that the phenomenon of rapidly triggered caspase activation in the adult rat brain after transient forebrain ischemia is specific to mature neurons and does not occur in neuroprogenitor cells or immature neurons...
  11. ncbi request reprint Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosis
    Robert W Neumar
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    J Biol Chem 278:14162-7. 2003
    ..Subsequent calpain activity, facilitated by caspase-mediated degradation of calpastatin, contributes to plasma membrane disruption and secondary necrosis...
  12. pmc Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest
    Robert Siman
    Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Brain Res 1213:1-11. 2008
    ....
  13. pmc A panel of neuron-enriched proteins as markers for traumatic brain injury in humans
    Robert Siman
    Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurotrauma 26:1867-77. 2009
    ..Our results identify neuron-enriched proteins that may serve as a panel of CSF and blood surrogate markers for the minimally invasive detection, management, mechanistic, and therapeutic evaluation of human TBI...
  14. ncbi request reprint Caspase-mediated cell death predominates following engraftment of neural progenitor cells into traumatically injured rat brain
    Asha Bakshi
    Traumatic Brain Injury Laboratory, Department of Neurosurgery, Philadelphia, PA 19104, USA
    Brain Res 1065:8-19. 2005
    ..These results suggest that both the caspase and calpain family of proteases are involved in graft cell death, and that caspase-mediated apoptotic graft cell death predominates in the acute post-traumatic period following TBI...
  15. ncbi request reprint Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia
    Chen Zhang
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Neurobiol Dis 10:289-05. 2002
    ....
  16. ncbi request reprint E2F1 induces cell death, calpain activation, and MDMX degradation in a transcription independent manner implicating a novel role for E2F1 in neuronal loss in SIV encephalitis
    Gordon D Strachan
    Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6030, USA
    J Cell Biochem 96:728-40. 2005
    ..Together these experiments support a new function for E2F1 in the activation of calpain proteases and suggest a role for this pathway in SIVE...
  17. ncbi request reprint Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice
    Gulyeter Serbest
    Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA
    Neurochem Res 32:2006-14. 2007
    ..Protection of the axonal cytoskeleton represents a potential therapeutic target for axonal damage associated with injury or neurodegenerative diseases...
  18. ncbi request reprint Caspase-3 activation in oligodendrocytes from the myelin-deficient rat
    J S Beesley
    Department of Neurology Research, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    J Neurosci Res 64:371-9. 2001
    ..These results suggest that mutant PLP affects not only cell death but also oligodendrocyte differentiation...
  19. pmc Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit
    Catherine R von Reyn
    Departments of Bioengineering, Pharmacology, Neurosurgery, Emergency Medicine, and Neuroscience, University of Pennsylvania, Philadelphia, PA 19104 6321, USA
    J Neurosci 29:10350-6. 2009
    ....
  20. pmc Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease
    Chen Zhang
    Laboratory for Neurodegeneration, Center for Brain Injury and Repair, University of Pennsylvania School of Medicine, 105B Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104, USA
    Exp Neurol 204:77-87. 2007
    ....
  21. ncbi request reprint Neuroprotection with delayed initiation of prolonged hypothermia after in vitro transient global brain ischemia
    Eric J Lawrence
    Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 4283, USA
    Resuscitation 64:383-8. 2005
    ..These results suggest the need for further in vivo studies to define the therapeutic window within which prolonged hypothermia is optimally neuroprotective after cardiac arrest...
  22. ncbi request reprint Calpain facilitates the neuron death induced by 3-nitropropionic acid and contributes to the necrotic morphology
    Zhen Pang
    Sanders Brown Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, KY 40536 0230, USA
    J Neuropathol Exp Neurol 62:633-43. 2003
    ..Together, the results indicate that following 3NP administration, increased calpain activity precedes caspase-3 activation, contributes to the necrotic morphology, and facilitates and accelerates the cell death...
  23. ncbi request reprint FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction
    Dorothy G Flood
    Department of Neurobiology, Cephalon, Inc, West Chester, PA 19380, USA
    Neurobiol Aging 23:335-48. 2002
    ..The APP(NLh/NLh)/PS-1(P264L/P264L) double gene-targeted mouse represents an animal model that exhibits Abeta deposition without overexpression of APP...
  24. ncbi request reprint A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 114:635-45. 2003
    ..These data raise the possibility that FAD mutation-induced transcriptional abnormalities maybe causally related to the dementia associated with FAD...
  25. ncbi request reprint Distinct nuclear and cytoplasmic localization of caspase cleavage products in two models of induced apoptotic death in dopamine neurons of the substantia nigra
    Tinmarla F Oo
    Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Exp Neurol 175:1-9. 2002
    ..It will be important to recognize these differences in the consideration of caspase inhibitors in the treatment of degenerative neurologic disease...
  26. ncbi request reprint Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct pathways of cell death after neonatal hypoxic-ischemic brain injury
    Byung Hee Han
    Department of Neurology, Washington University, St Louis, Missouri 63110, USA
    J Biol Chem 277:30128-36. 2002
    ....

Research Grants1

  1. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2007
    ..The proposed research will advance our understanding of pathogenic mechanisms of FAD-linked gene mutations and evaluate therapeutic strategies aimed at slowing the onset and progression in a faithful mouse genetic model of FAD. ..