Affiliation: University of Pennsylvania
- Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerabilityR 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...
- Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutationR Siman
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 276:44736-43. 2001....
- Novel surrogate markers for acute brain damage: cerebrospinal fluid levels corrrelate with severity of ischemic neurodegeneration in the ratRobert 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...
- Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brainR 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...
- Proteins released from degenerating neurons are surrogate markers for acute brain damageRobert Siman
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
Neurobiol Dis 16:311-20. 2004....
- Localization of presenilin-nicastrin complexes and gamma-secretase activity to the trans-Golgi networkRobert 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...
- Calpain activity in the rat brain after transient forebrain ischemiaR W Neumar
Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA
Exp Neurol 170:27-35. 2001....
- Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit compositionMichael 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....
- Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain traumaXiao 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...
- Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activationZhaoming 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...
- Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosisRobert 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...
- Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrestRobert Siman
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Brain Res 1213:1-11. 2008....
- A panel of neuron-enriched proteins as markers for traumatic brain injury in humansRobert 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...
- Caspase-mediated cell death predominates following engraftment of neural progenitor cells into traumatically injured rat brainAsha 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...
- Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemiaChen Zhang
Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Neurobiol Dis 10:289-05. 2002....
- 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 encephalitisGordon 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...
- Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in miceGulyeter 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...
- Caspase-3 activation in oligodendrocytes from the myelin-deficient ratJ 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...
- Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunitCatherine 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....
- Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's diseaseChen 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....
- Neuroprotection with delayed initiation of prolonged hypothermia after in vitro transient global brain ischemiaEric 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...
- Calpain facilitates the neuron death induced by 3-nitropropionic acid and contributes to the necrotic morphologyZhen 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...
- FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproductionDorothy 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...
- A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutationsPhilippe 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...
- Distinct nuclear and cytoplasmic localization of caspase cleavage products in two models of induced apoptotic death in dopamine neurons of the substantia nigraTinmarla 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...
- Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct pathways of cell death after neonatal hypoxic-ischemic brain injuryByung Hee Han
Department of Neurology, Washington University, St Louis, Missouri 63110, USA
J Biol Chem 277:30128-36. 2002....
- PATHOGENIC MECHANISMS OF PRESENILIN MUTATIONRobert 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. ..