Genomes and Genes
M S Shearman
Affiliation: Merck Research Laboratories
- Cellular MTT reduction distinguishes the mechanism of action of beta-amyloid from that of tachykinin receptor peptidesM S Shearman
Merck Sharp and Dohme Research Laboratories Neuroscience Research Centre, Harlow, Essex, UK
Neuropeptides 30:125-32. 1996....
- L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activityM S Shearman
Department of Molecular Biology, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, England
Biochemistry 39:8698-704. 2000..Specific and potent inhibitors of A beta PP gamma-secretase activity such as L-685,458 will enable important advances toward the identification and elucidation of the mechanism of action of this enigmatic protease...
- Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding siteN J Brandon
Merck Sharp and Dohme Research Labs, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK
Mol Cell Neurosci 28:613-24. 2005....
- Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma -secretase inhibitor: implications for presenilin biologyD Beher
Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom
J Biol Chem 276:45394-402. 2001..Even though the beta-amyloid precursor protein cleavage and the S3 cleavage of the Notch receptor are inhibited by CBAP, an impairment of Trk receptor maturation was not observed...
- Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitorS Grimwood
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
Neuropharmacology 48:1002-11. 2005....
- Quantitation of amyloid-beta peptides in biological milieu using a novel homogeneous time-resolved fluorescence (HTRF) assayE E Clarke
Department of Molecular Biology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK
J Neurosci Methods 102:61-8. 2000....
- Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disordersN J Brandon
Merck Sharp and Dohme, The Neuroscience Research Centre, Harlow, Essex, CM20 2QR, UK
Mol Cell Neurosci 25:42-55. 2004....
- Gamma-secretase inhibitionD Beher
Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK
Biochem Soc Trans 30:534-7. 2002....
- Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementiaH Lewis
Department of Molecular and Cellular Neuroscience, Merck, Sharp and Dohme Research Laboratories, Terlings Park, Essex
Neuropathol Appl Neurobiol 32:103-18. 2006..Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age...
- Endoproteolysis of the ER stress transducer ATF6 in the presence of functionally inactive presenilinsH Steiner
Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, 80036 Munich, Germany
Neurobiol Dis 8:717-22. 2001..This finding indicates that gamma-secretase inhibitors, which are currently developed as therapeutic agents to lower the A beta burden in brains of AD patients, do not interfere with the UPR response...
- Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formationF G Gervais
Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Kirkland, Quebec, Canada
Cell 97:395-406. 1999..Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease...
- Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and gamma-secretase activityA L Brunkan
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Neurochem 94:1315-28. 2005....
- The C-terminal fragment of the Alzheimer's disease amyloid protein precursor is degraded by a proteasome-dependent mechanism distinct from gamma-secretaseJ Nunan
Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
Eur J Biochem 268:5329-36. 2001..These results raise the possibility that defective proteasome function could lead to an increase in Abeta production in the AD brain...