J Steven Jacobsen
Affiliation: Wyeth Research
- Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's diseaseThomas A Comery
Discovery Neuroscience, Wyeth Research, CN8000, Princeton, New Jersey 08543, USA
J Neurosci 25:8898-902. 2005..Furthermore, they suggest that acute treatment with GSI may provide improved cognitive functioning as well as disease-modifying effects in Alzheimer's disease...
- Alzheimer's disease: an overview of current and emerging therapeutic strategiesJ Steven Jacobsen
Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, New Jersey, 08543 8000, USA
Curr Top Med Chem 2:343-52. 2002....
- Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascadeJ Steven Jacobsen
Departments of Discovery Neuroscience and Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
Proc Natl Acad Sci U S A 105:8754-9. 2008....
- Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's diseaseJ Steven Jacobsen
Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
Proc Natl Acad Sci U S A 103:5161-6. 2006..Overall, these data show that the perforant path input from the entorhinal cortex to the DG is compromised both structurally and functionally, and this pathology is manifested in memory defects long before significant plaque deposition...
- Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's diseaseRobert L Martone
Wyeth Research, Departments of Discovery Neuroscience, Princeton, New Jersey 08543, USA
J Pharmacol Exp Ther 331:598-608. 2009..In healthy human volunteers, oral administration of a single dose of GSI-953 produces dose-dependent changes in plasma Abeta levels, confirming pharmacodynamic activity of GSI-953 in humans...
- (S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing gamma-secretase inhibitorDerek C Cole
Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 19:926-9. 2009..5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (Abeta(40/42) EC(50)=28 nM), which is efficacious in reduction of Abeta production in vivo...
- Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's diseaseScott C Mayer
Chemical and Screening Sciences, and Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA
J Med Chem 51:7348-51. 2008..Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5), which was selected for development for the treatment of Alzheimer's disease...
- Functional characterization of Narc 1, a novel proteinase related to proteinase KSaule Naureckiene
Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
Arch Biochem Biophys 420:55-67. 2003....
- Expression of NALP1 in cerebellar granule neurons stimulates apoptosisFeng Liu
Wyeth Neuroscience Discovery Research, CN 8000, Princeton, NJ 08543, USA
Cell Signal 16:1013-21. 2004..Also described here are studies on the mechanism of action studies including deletion analyses and investigations of nucleotide binding, which begin to elucidate a regulatory function for NALP1 in neuronal apoptosis...
- Current concepts in therapeutic strategies targeting cognitive decline and disease modification in Alzheimer's diseaseJ Steven Jacobsen
Wyeth Research, Neuroscience Discovery, CN8000, Princeton, New Jersey 08543, USA
NeuroRx 2:612-26. 2005....
- Proapoptotic effects of NARC 1 (= PCSK9), the gene encoding a novel serine proteinaseBrendan Bingham
Neuroscience Discovery Research, Wyeth Research, Princeton, New Jersey 08543 8000, USA
Cytometry A 69:1123-31. 2006..Coregulation of known apoptotic mediators (caspase-3 and death receptor 6) raises the possibility that NARC 1 might be involved in the propagation of apoptotic signaling in neurons...
- Antibody capture of soluble Abeta does not reduce cortical Abeta amyloidosis in the PDAPP mousePeter Seubert
Elan Pharmaceuticals, Inc, South San Francisco, Calif 94080, USA
Neurodegener Dis 5:65-71. 2008....