Presenilin and γ-secretase: Structure meets function

Journal of Neurochemistry

Volumn 76, Issue 6, 2001, Pages 1615-1620

  Wolfe, Michael S ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; GAMMA SECRETASE; NOTCH RECEPTOR; PRESENILIN 1; PRESENILIN 2;

ALZHEIMER DISEASE; CARBOXY TERMINAL SEQUENCE; ENZYME ACTIVITY; ENZYME SPECIFICITY; EXON; HUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; RNA SPLICING; SHORT SURVEY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; CELL MEMBRANE; ENDOPEPTIDASES; HUMANS; MEMBRANE PROTEINS; PRESENILIN-1; PRESENILIN-2; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, NOTCH;

EID: 0035106128     PISSN: 00223042     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1471-4159.2001.00245.x     Document Type: Short Survey

References (62)

1. Aspartate mutations in presenilin and γ-secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch1 signaling
2. A novel proteolytic cleavage involved in Notch signaling: The role of the disintegrin-metalloprotease TACE
3. Evidence that tumor necrosis factor ct converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer's amyloid protein precursor
4. Release of excess amyloid beta protein from a mutant amyloid beta protein precursor
5. The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex
6. Presenilin-1 differentially facilitates endoproteolysis of the beta-amyloid precursor protein and Notch
7. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene
8. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production
9. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation
10. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice
11. Alzheimer's disease. A firm base for drug development
12. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
13. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
14. The seven-transmembrane spanning topography of the Alzheimer disease-related presenilin proteins in the plasma membranes of cultured cells
15. Protein topology of presenilin 1
16. Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1
17. Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
18. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
19. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid beta-protein precursor
20. The Alzheimer family of diseases: Many etiologies, one pathogenesis?
21. Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells
22. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1
23. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease
24. The transmembrane aspartates in presenilin 1 and 2 are obligatory for γ-secretase activity and amyloid β-protein generation
25. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease
26. The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases
27. Evidence for a six-transmembrane domain structure of presenilin 1
28. Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide production and requires a critical aspartate residue for its function in amyloidogenesis
29. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans
30. Candidate gene for the chromosome 1 familial Alzheimer's disease locus
31. Membrane topology of the C. elegans SEL-12 presenilin
32. HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling
33. Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins
34. Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state
35. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1
36. Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana
37. The Notch1 receptor is cleaved constitutively by a furin-like convertase
38. A ligand-induced extracellular cleavage regulates-secretase-like proteolytic activation of Notch1
39. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease
40. Effects of PS1 deficiency on membrane protein trafficking in neurons
41. Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue
42. Endoproteolytic processing and stabilization of wild-type and mutant presenilin
43. Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs
44. Cell surface presenilin-1 participates in the γ-secretase-like proteolysis of Notch
45. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
46. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease
47. In search of gamma-secretase: Presenilin at the cutting edge. Proc
48. Cloning of a gene beating missense mutations in early-onset familial Alzheimer's disease
49. Purification and cloning of amyloid precursor protein beta-secretase from human brain
50. Expression of Alzheimer's disease-associated presenilin-1 is controlled by proteolytic degradation and complex formation
51. A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling
52. The biological and pathological function of the presenilin-1 Δexon 9 mutation is independent of its defect to undergo proteolytic processing
53. Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis
54. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP. 717) mutants
55. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo
56. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors
57. Peptidomimetic probes and molecular modeling suggest Alzheimer's γ-secretases are intramembrane-cleaving aspartyl proteases
58. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
59. Mutation of conserved aspartates affect maturation of both aspartate-mutant and endogenous presenilin 1 and presenilin 2 complexes
60. Membrane topology of S2P, a protein required for intramembranous cleavage of sterol regulatory element-binding proteins
61. Subcellular distribution and turnover of presenilins in transfected cells
62. Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1