Affiliation: University of Pittsburgh
- Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathyWesley Farris
Center for Neurologic Diseases, Department of Neurology, Harvard Institutes of Medicine, Room 730, Boston, MA 02115, USA
Am J Pathol 171:241-51. 2007....
- Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature deathMalcolm A Leissring
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
Neuron 40:1087-93. 2003..Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo...
- Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-proteinWesley Farris
Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Am J Pathol 164:1425-34. 2004..Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD...
- Alternative splicing of human insulin-degrading enzyme yields a novel isoform with a decreased ability to degrade insulin and amyloid beta-proteinWesley Farris
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Biochemistry 44:6513-25. 2005..Our results identify a novel, catalytically inefficient form of IDE expressed in brain and non-neural tissues and recommend novel regions of the IDE gene in which to search for mutations predisposing patients to AD and DM2...
- Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid beta-protein metabolism in mouse models of Alzheimer diseaseMatthew L Hemming
Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
Neurobiol Dis 26:273-81. 2007..Furthermore, we find no change in plaque deposition or in peripheral Abeta levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause Abeta accumulation in vivo...
- Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondriaMalcolm A Leissring
Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
Biochem J 383:439-46. 2004..Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria...
- Kinetics of amyloid beta-protein degradation determined by novel fluorescence- and fluorescence polarization-based assaysMalcolm A Leissring
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
J Biol Chem 278:37314-20. 2003..The use of these assays should yield additional new insights into the biology of Abeta-degrading proteases and facilitate the identification of activators and inhibitors of such enzymes...
- Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivoWesley Farris
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4162-7. 2003....
- Effects of chronic glucocorticoid administration on insulin-degrading enzyme and amyloid-beta peptide in the aged macaqueJ Jacob Kulstad
Geriatric Research, Education, and Clinical Center, Veteran s Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA
J Neuropathol Exp Neurol 64:139-46. 2005..These findings support the notion that glucocorticoids regulate IDE and provide a mechanism whereby increased glucocorticoid levels may contribute to AD pathology...
- Role of ABeta-Degrading Proteases in Alzheimer's DiseaseWesley Farris; Fiscal Year: 2007..The candidate's career development plan, world-class training environment, and commitment from his Department will allow the realization of this goal. ..