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Wolfe Laboratory
--Selected Publications--

Selected Research Reports

Wolfe MS, Citron M, Diehl TS, Xia W, Donkor IO, Selkoe DJ. “ A substrate-based difluoroketone selectively inhibits Alzheimer’s g-Secretase Activity.” J. Biol. Chem., 1998; 41:6-9.

Wolfe MS, Xia W, Moore CL, Leatherwood DD, Ostaszewski B, Rahmati T, Donkor IO, and Selkoe DJ. “Peptidomimetic Probes and molecular modeling suggest that Alzheimer’s gamma-secretase is an intramembrane-cleaving aspartyl protease.” Biochemistry 1999, 38, 4720-7.

Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberley TS, and Selkoe DJ. “Two Transmembrane aspartates in presenilin- 1 required for presenilin endoproteolysis and gamma-secretase activity.” Nature 1999, 398, 513-7.

Esler WP, Kimberly WT, Ostaszewski BL, Diehl TS, Moore CL, Tsai J-Y, Rahmati T, Xia W, Selkoe DJ, and Wolfe MS. “Transition-State Analogue inhibitors of gamma-secretase bind directly to presenilin-1.” Nature Cell Biology 2000,2(7), 428-34.

Esler WP, Kimberly WT, Ostaszewski BL, Ye W, Diehl TS, Selkoe DJ, and Wolfe MS. “Activity-dependent isolation of the presenilin/gamma-secretase complex reveals nicastrin and a gamma substrate.” Proc. Natl. Acad. Sci. USA 2002, 99, 2720-5.

Micchelli CA, Esler WP, Kimberly WT, Jack C, Berezovska O, Kornilova A, Hyman BT, Perrimon N, and Wolfe MS. “gamma-secretase/presenilin inhibitors for Alzheimer’s disease phenocopy Notch mutations in Drosophila.” FASEB J, 2003, 17, 79-81.

Kimberly WT, Esler WP, Ye W, Ostaszewski BL, Gao J, Diehl TS, Selkoe DJ, and Wolfe MS. “Notch and amyloid precursor protein are cleaved by similar gamma-secretase(s).” Biochemistry, 2003, 42, 137-44.

Kornilova AY, Das C, and Wolfe MS.  "Differential effects of inhibitors on the gamma-secretase complex: mechanistic implications.”  J. Biol. Chem., 2003, 278, 16470-3.

Kimberly WT, Ostaszewski BL, Ye W, LaVoie MJ, Wolfe MS and Selkoe DJ.  "Gamma-Secretase is a membrane protein complex of presenilin, nicastrin, aph-1 and pen-2.   Proc. Natl. Acad. Sci. USA, 2003, 100, 6382-6387.

Das C, Berezovska O, Diehl TS, Genet C, Buldyrev I, Tsai JY, Hyman BT, Wolfe MS. “Designed helical peptides inhibit an intramembrane protease.”Biochemistry, 2003, 42, 137-44.

Fraering PC, LaVoie MJ, Ye W, Ostaszewski BL, Kimberly WT, Selkoe DJ, Wolfe MS. “Detergent-dependent dissociation of active g-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex.” Biochemistry, 2004; 43: 323-33.

Fraering PC, Ye W, Strub JM, Dolios G, LaVoie MJ, Ostaszewski BL, van Dorsselaer A, Wang R, Selkoe DJ, Wolfe MS. “ Purification and characterization of the human g-secretase complex.” Biochemistry, 2004; 43: 9774-89.

Bihel F, Das C, Bowman MJ, Wolfe MS. “ Discovery of a subnanomolar helical D-tridecapeptide inhibitor of g-secretase.” J. Med. Chem., 2004; 47: 3931-3.

Urban S and Wolfe MS. “ Reconstitution of intramembrane proteolysis in vitro reveals pure rhomboid is sufficient for catalysis and specificity.” Proc. Natl. Acad. Sci. USA, 2005; 102:6, 1883-8.

Kornilova AY, Bihel F, Das C and Wolfe MS. “ The initial substrate binding site of g-secretase is located on presenilin near the active site.” Proc. Natl. Acad. Sci. USA, 2005; 102:9, 3230-5.

Fraering PC, Ye W, Lavoie MJ, Ostaszewski BL, Selkoe DJ, Wolfe MS.g -Secretase substrate selectivity can be modulated directly via interaction with a nucleotide binding site.” J. Biol. Chem., 2005; 280(51):41987-96.

Lazarov VK, Fraering PC, Ye W, Wolfe MS, Selkoe DJ, Li H. “ Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores.” Proc. Natl. Acad. Sci. USA, 2006; 103(18):6889-94.

Kornilova AY, Kim J, Laudon H, Wolfe MS. “ Deducing the transmembrane domain organization of presenilin-1 in g-secretase by cysteine disulfide crosslinking.” Biochemistry, 2006; 45(24):7598-604.

Sato T, Nyborg AC, Iwata N, Diehl TS, Saido TC, Golde TE, Wolfe MS. “ Signal peptide peptidase: biochemical properties and modulation by nonsteroidal anti-inflammatory drugs.” Biochemistry, 2006; 45(28):8649-56.

Donahue CP, Muratore C, Wu J, Kosik KS, Wolfe MS. “ Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing.” J. Biol. Chem., 2007, 281(33): 23303-06.

Narayanan S, Sato T, Wolfe MS. “ A C-terminal region of signal peptide peptidase defines a functional domain for intramembrane aspartyl protease catalysis.” J. Biol. Chem., 2007, 282(28): 20172-9.

Selected Reviews and Book Chapters

Esler WP and Wolfe MS. “Portraits of Alzheimer secretases: new features and familiar faces.” Science 2001, 293, 1449-54.

Wolfe MS. “Therapeutic strategies for Alzheimer’s disease.” Nature Reviews Drug Discovery 2002,1, 859-66.

Wolfe MS, Kopan R. “Intramembrane proteolysis: Theme and variations.” Science 2004; 305: 1119-1123

Wolfe MS. “Shutting Down Alzheimer's” Scientific American, May 2006, 72-9