M S Wolfe
Affiliation: Harvard University
- Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's diseaseM S Wolfe
Department of Pharmaceutical Sciences, University of Tennessee, Memphis 38163, USA
Biochemistry 38:11223-30. 1999..Thus, presenilins and S2P appear to be members of a new type of polytopic protease with an intramembranous active site...
- FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a gamma-secretase inhibitor: evidence for direct involvement of PS1 in the gamma-secretase cleavage complexW Xia
Department of Neurology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Neurobiol Dis 7:673-81. 2000..Taken together, these findings suggest that PS1 participates physically in a complex with APP during the gamma-secretase cleavage event...
- gamma-Secretase inhibitors as molecular probes of presenilin functionM S Wolfe
Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
J Mol Neurosci 17:199-204. 2001..Heterodimeric presenilin appears to be the catalytic portion of a multi-protein gamma-secretase complex...
- Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generationW Xia
Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 97:9299-304. 2000..Thus, PSs are complexed with the gamma-secretase substrates C83 and C99 in the subcellular locations where Abeta is generated, indicating that PSs are directly involved in the pathogenically critical intramembranous proteolysis of APP...
- Rapid Notch1 nuclear translocation after ligand binding depends on presenilin-associated gamma-secretase activityO Berezovska
Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA
Ann N Y Acad Sci 920:223-6. 2000....
- CYP1A2 and CYP2D6 4-hydroxylate propranolol and both reactions exhibit racial differencesJ A Johnson
College of Pharmacy, University of Tennessee, Memphis, USA
J Pharmacol Exp Ther 294:1099-105. 2000..The observed racial differences in drug metabolism may have relevance to drug efficacy, toxicity, or carcinogen activation for CYP1A2 or CYP2D6 substrates...
- A portrait of Alzheimer secretases--new features and familiar facesW P Esler
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Science 293:1449-54. 2001..Identification of the alpha-, beta-, and gamma-secretases provides potential targets for designing new drugs to treat AD...
- Gamma -secretase inhibitors repress thymocyte developmentB K Hadland
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA
Proc Natl Acad Sci U S A 98:7487-91. 2001....
- Effect of PS1 deficiency and an APP gamma-secretase inhibitor on Notch1 signaling in primary mammalian neuronsC Jack
Alzheimer s Disease Research Laboratory, Department of Neurology, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA
Brain Res Mol Brain Res 87:166-74. 2001..These results support the hypothesis that PS1 deficiency blocks neuronal Notch1 processing and signaling...
- Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activityM S Wolfe
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Nature 398:513-7. 1999....
- Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signalingO Berezovska
Alzheimer s Disease Research Laboratory, Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Charlestown, California, USA
J Neurochem 75:583-93. 2000..The latter is an important finding from the perspective of therapeutic treatment of Alzheimer's disease by targeting gamma-secretase processing of APP to reduce Abeta production...
- The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generationW T Kimberly
Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
J Biol Chem 275:3173-8. 2000..We conclude that presenilins, and their TM aspartates in particular, are attractive targets for lowering Abeta therapeutically to prevent Alzheimer's disease...
- A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domainB De Strooper
Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology VIB4, Center for Human Genetics, KU Leuven, Belgium
Nature 398:518-22. 1999..Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling...
- Notch-Delta signaling is required for spatial patterning and Müller glia differentiation in the zebrafish retinaR L Bernardos
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109 0616, USA
Dev Biol 278:381-95. 2005..In contrast to neurons, Müller glia failed to differentiate suggesting an instructive role for Notch-Delta signaling in gliogenesis...