Genomes and Genes
Affiliation: Harvard University
- 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....
- 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...
- Notch1 and amyloid precursor protein are competitive substrates for presenilin1-dependent gamma-secretase cleavageO Berezovska
Alzheimer's Disease Research Laboratory, Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Biol Chem 276:30018-23. 2001..In summary, two complementary approaches suggest that APP and Notch1 are physiologically relevant competitive substrates for gamma-secretase activity...
- 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...
- Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleusA Kinoshita
Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
J Neurochem 82:839-47. 2002..Visualization of the APP-CT-Fe65 complex in the nucleus may serve as a readout for processes that modify gamma secretase release of APP-CT...
- Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptideL Puglielli
Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Building 114, 16th Street, Charlestown, Massachusetts 02129-4404, USA
Nat Cell Biol 3:905-12. 2001..We also show that pharmacological inhibitors of ACAT, developed for the treatment of atherosclerosis, are potent modulators of Abeta generation, indicating their potential for use in the treatment of Alzheimer's disease...
- Biochemical and immunocytochemical characterization of calsenilin in mouse brainN F Zaidi
Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA
Neuroscience 114:247-63. 2002..Finally, the expression pattern of calsenilin, which is similar to that of the presenilin(s), suggests that the common locations of these two proteins provide an opportunity for physical interaction in vivo...
- Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer diseaseO Berezovska
Alzheimer Research Unit, Massachusetts General Hospital, Charlestown 02129, USA
J Neuropathol Exp Neurol 57:738-45. 1998..The alteration in Notch1 expression in sporadic Alzheimer disease raises the possibility that disruption of Notch1/PS-1 functional interactions may occur in Alzheimer disease...
- Developmental regulation of presenilin mRNA expression parallels notch expressionO Berezovska
Alzheimer Research Unit, Laboratory of Genetics and Aging, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
J Neuropathol Exp Neurol 56:40-4. 1997..These observations show that, like Notch, PS1 and PS2 are strongly developmentally regulated, and support the plausibility of an interaction between PSs and Notch...