pic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci U S A 103: 68896894. 29. Osenkowski P, Li H, Ye W, Li D, Aeschbach L, et al. Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J Mol Biol 385: 642652. 30. Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, et al. 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. Proc Natl Acad Sci U S A 96: 1187211877. 31. Herreman A, Van Gassen G, Bentahir M, Nyabi O, Craessaerts K, et al. gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation. J Cell Sci 116: 11271136. 32. Nyabi O, Bentahir M, Horre K, Herreman A, 606143-89-9 Gottardi-Littell N, et al. Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 12 Purified c-Secretase Complexes with PS1 Mutations 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin. J Biol Chem 278: 4343043436. Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17: 181190. Nelson O, Tu H, Lei T, Bentahir M, de Strooper B, et al. Familial Alzheimer disease-linked mutations specifically disrupt ” Ca2+ leak function of presenilin 1. J Clin Invest 117: 12301239. Heilig EA, Xia W, Shen J, Kelleher RJ A presenilin-1 mutation identified in familial Alzheimer’s disease with cotton wool plaques causes nearly complete loss of -secretase activity. J Biol Chem. Lichtenthaler SF, Multhaup G, Masters CL, Beyreuther K A novel substrate for analyzing Alzheimer’s disease gamma-secretase. FEBS letters 453: 288292. Fraering PC, LaVoie MJ, Ye W, Ostaszewski BL, Kimberly WT, et al. Detergent-dependent dissociation of active gamma-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex. Biochemistry 43: 323333. Duff K, Eckman C, Zehr C, Yu X, Prada CM, et al. Increased amyloidbeta42 in brains of mice expressing mutant presenilin 1. Nature 383: 710713. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, et al. Visualization of A beta 42 and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42. Neuron 13: 4553. Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, et al. Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J Biol Chem 267: 546554. Jan A, Gokce O, Luthi-Carter R, Lashuel HA The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. J Biol Chem 283: 2817628189. Jarrett JT, Berger EP, Lansbury PT, Jr. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease. Biochemistry 32: 46934697. Scheuner D, Eckman C, Jensen M, Song X, Citron M, et al. Secreted amyloid beta-protein “2436504 similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s dise
Posted inUncategorized