The cell biology of Alzheimer's disease: Uncovering the secrets of secretases

Current Opinion in Neurobiology

Volumn 11, Issue 5, 2001, Pages 585-590

  Walter, J ^a   Kaether, C ^a   Steiner, H ^a   Haass, C ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

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

ALZHEIMER DISEASE; BRAIN; CYTOLOGY; DRUG DESIGN; ENZYME ACTIVITY; HUMAN; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW;

EID: 0035477333     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(00)00253-1     Document Type: Review

References (67)

1. Alzheimer's disease: Genes, proteins, and therapy
2. Mechanisms of neuronal degeneration in Alzheimer's disease
3. Molecular genetics of Alzheimer's disease: The role of β-amyloid and the presenilins
4. Amyloid β-protein and the genetics of Alzheimer's disease
5. Amyloid fibrillogenesis: Themes and variations
6. Amyloid diseases: Abnormal protein aggregation in neurodegeneration
7. Intramembrane proteolysis by presenilins
8. Evidence that tumor necrosis factor-α converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor
9. Constitutive and regulated α-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease
10. Purification and cloning of amyloid precursor protein β-secretase from human brain
11. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
12. Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity
13. Identification of a novel aspartic protease (Asp 2) as β-secretase
14. Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein
15. Expression analysis of BACE2 in brain and peripheral tissues
16. Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation
17. BACE1 is the major β-secretase for generation of Aβ peptides by neurons
18. BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein
19. Aβ-generating enzymes: Recent advances in β- and γ-secretase research
20. In search of an enzyme: The β-secretase of Alzheimer's disease is an aspartic proteinase
21. Characterization of Alzheimer's β-secretase protein BACE. A pepsin family member with unusual properties
22. Maturation and pro-peptide cleavage of β-secretase
23. A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's β-secretase
24. Post-translational processing of β-secretase (β-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-β production
25. Processing of β-secretase (Bace) by furin and other members of the proprotein convertase family
26. The pro domain of β-secretase does not confer strict zymogen-like properties but does assist proper folding of the protease domain
27. Phosphorylation regulates intracellular trafficking of β-secretase
28. Maturation and endosomal targeting of β-site amyloid precursor protein-cleaving enzyme. The Alzheimer's disease β-secretase
29. Presenilins are required for γ-secretase cleavage of β-APP and transmembrane cleavage of Notch-1
30. Total inactivation of γ-secretase activity in presenilin-deficient embryonic stem cells
31. Nicastrin modulates presenilin-mediated Notch/glp-1 signal transduction and βAPP processing
32. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
33. Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases
34. Notch signaling: From the outside in
35. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
36. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency
37. A loss of function mutation of presenilin-2 interferes with amyloid β-peptide production and Notch signaling
38. Cell surface presenilin-1 participates in the γ-secretase-like proteolysis of Notch
39. An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos
40. Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Aβ1-42/43 expression
41. Human presenilin-1, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing
42. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans
43. Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations
44. Presenilin-1 mutations reduce cytoskeletal association, deregulate neurite growth, and potentiate neuronal dystrophy and tau phosphorylation
45. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein
46. Evidence that production and release of amyloid β-protein involves the endocytic pathway
47. Identification of the Alzheimer β/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells
48. Mutagenesis identifies new signals for β-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Aβ42
49. Targeting of cell-surface β-amyloid precursor protein to lysosomes: Alternative processing into amyloid-bearing fragments
50. Trafficking of cell-surface amyloid β-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization
51. Trafficking of cell-surface amyloid β-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody
52. Metabolism of the 'Swedish' amyloid precursor protein variant in Madin-Darby canine kidney cells
53. The Swedish mutation causes early-onset Alzheimer's disease by β-secretase cleavage within the secretory pathway
54. Alzheimer's Aβ(1-42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells
55. Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides
56. Intracellular generation and accumulation of amyloid β-peptide terminating at amino acid 42
57. The Alzheimer's disease-associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum
58. Presenilin 1 controls γ-secretase processing of amyloid precursor protein in pre-Golgi compartments of hippocampal neurons
59. The multiple paradoxes of presenilins
60. Endogenous presenilin-1 targets to endocytic rather than biosynthetic compartments
61. Gamma-secretase inhibitors repress thymocyte development
62. Notch as a mediator of cell fate determination in hematopoiesis: Evidence and speculation
63. Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor
64. A novel γ-secretase assay based on detection of the putative C-terminal fragment-γ of amyloid β protein precursor
65. Distinct intramembrane cleavage of the β-amyloid precursor protein family resembling γ-secretase-like cleavage of Notch
66. Presenilin dependent γ-secretase processing of β-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch
67. A transcriptional active complex of APP with Fe65 and histone acetyltransferase Tip60