γ-secretase inhibitors as molecular probes of presenilin function

Journal of Molecular Neuroscience

Volumn 17, Issue 2, 2001, Pages 199-204

  Wolfe, M S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Alzheimer's disease; Amyloid; Amyloid precursor protein; Notch; Protease

Indexed keywords

AMYLOID BETA PROTEIN; ASPARTIC ACID; ASPARTIC PROTEINASE; ENZYME INHIBITOR; GAMMA SECRETASE; INDINAVIR; MEMBRANE PROTEIN; NELFINAVIR; NOTCH RECEPTOR; PEPSTATIN; PRESENILIN 1; PRESENILIN 2; PROTEINASE; RENIN INHIBITOR; SERPENTINE;

ALZHEIMER DISEASE; ARTICLE; BINDING AFFINITY; CATALYSIS; ENZYME ACTIVITY; GENE MUTATION; HUMAN; PROTEIN DEGRADATION;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; ENDOPEPTIDASES; HUMANS; MEMBRANE PROTEINS; PRESENILIN-1;

EID: 0035168209     PISSN: 08958696     EISSN: None     Source Type: Journal    
DOI: 10.1385/JMN:17:2:199     Document Type: Article

References (40)

1. Aspartate mutations in presenilin and γ-secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notchl signaling
2. Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities
3. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
4. Alzheimer's disease. A firm base for drug development
5. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
6. Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1
7. Design of potent inhibitors for human brain memapsin 2 (beta-secretase)
8. Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism
9. Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor
10. HIV protease: A novel chemotherapeutic target for AIDS
11. Crystallographic analysis of transition state mimics bound to penicillopepsin: Difluorostatine- and difluorostatone-containing peptides
12. The carboxyl termini of beta-amyloid peptides 1-40 and 1-42 are generated by distinct gamma-secretase activities
13. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans
14. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene
15. Candidate gene for the chromosome 1 familial Alzheimer's disease locus
16. Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state
17. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin
18. Mode of inhibition of acid proteases by pepstatin
19. Difluoro Ketone Peptidomimetics Suggest a Large S1 Pocket for Alzheimer's γ-Secretase: Implications for inhibitor design
20. Effects of PS1 deficiency on membrane protein trafficking in neurons
21. Endoproteolytic processing and stabilization of wild-type and mutant presenilin
22. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type
23. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
24. Endogenous presenilin redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix
25. Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors
26. L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity
27. Skeletal and CNS defects in Presenilin-1-deficient mice
28. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
29. Inhibition and catalytic mechanism of HIV-1 aspartic protease
30. Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis
31. Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogues
32. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo
33. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors
34. A substrate-based difluoro ketone selectively inhibits Alzheimer's γ-secretase activity
35. Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease
36. The role of presenilins in gamma-secretase activity
37. Peptidomimetic probes and molecular modeling suggest Alzheimer's γ-secretases are intramembrane-cleaving aspartyl proteases
38. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
39. Participation of presenilin 2 in apoptosis: Enhanced basal activity conferred by an Alzheimer mutation
40. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm