Published in J Biol Chem on February 09, 2010
The many substrates of presenilin/γ-secretase. J Alzheimers Dis (2011) 2.02
γ-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1. J Biol Chem (2011) 0.98
Cellular mechanisms of γ-secretase substrate selection, processing and toxicity. Prog Neurobiol (2012) 0.92
Chemical Biology, Molecular Mechanism and Clinical Perspective of γ-Secretase Modulators in Alzheimer's Disease. Curr Neuropharmacol (2011) 0.89
Substrate recruitment of γ-secretase and mechanism of clinical presenilin mutations revealed by photoaffinity mapping. EMBO J (2016) 0.86
γ-Secretase inhibition of murine choroidal neovascularization is associated with reduction of superoxide and proinflammatory cytokines. Invest Ophthalmol Vis Sci (2012) 0.85
The very many faces of presenilins and the γ-secretase complex. Protoplasma (2013) 0.82
The γ-secretase complex: from structure to function. Front Cell Neurosci (2014) 0.81
Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis. J Cell Biol (2015) 0.79
Pen-2 is essential for γ-secretase complex stability and trafficking but partially dispensable for endoproteolysis. Biochemistry (2014) 0.78
Modulation of γ-secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer's disease. PLoS One (2012) 0.78
Nicastrin is required for APP but not Notch processing, while Aph-1 is dispensable for processing of both APP and Notch. J Neurochem (2015) 0.77
Targeting γ-secretase in breast cancer. Breast Cancer (Dove Med Press) (2012) 0.77
Fluorescent Analogue of Batimastat Enables Imaging of α-Secretase in Living Cells. ACS Chem Neurosci (2015) 0.75
Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature (1999) 8.28
The role of presenilin cofactors in the gamma-secretase complex. Nature (2003) 5.03
Nicastrin functions as a gamma-secretase-substrate receptor. Cell (2005) 4.64
Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A (2003) 3.36
beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell (1995) 3.33
Requirements for presenilin-dependent cleavage of notch and other transmembrane proteins. Mol Cell (2000) 2.98
Presenilin: running with scissors in the membrane. Cell (2007) 2.55
gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease. Science (2009) 2.43
Substrate specificity of gamma-secretase and other intramembrane proteases. Cell Mol Life Sci (2008) 2.29
The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. J Biol Chem (2003) 2.22
Purification and characterization of the human gamma-secretase complex. Biochemistry (2004) 2.18
Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate. Proc Natl Acad Sci U S A (2002) 2.16
Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol Cell Neurosci (1996) 2.15
Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J Biol Chem (2003) 1.83
Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. J Biol Chem (1999) 1.82
PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem (2003) 1.77
The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage. J Biol Chem (2003) 1.66
Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J Biol Chem (2008) 1.65
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 (2004) 1.61
The initial substrate-binding site of gamma-secretase is located on presenilin near the active site. Proc Natl Acad Sci U S A (2005) 1.59
Presenilin 1 regulates the processing of beta-amyloid precursor protein C-terminal fragments and the generation of amyloid beta-protein in endoplasmic reticulum and Golgi. Biochemistry (1998) 1.57
Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer disease. PLoS Med (2007) 1.55
Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease. Proc Natl Acad Sci U S A (1997) 1.48
Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. J Biol Chem (2002) 1.44
Identification of distinct gamma-secretase complexes with different APH-1 variants. J Biol Chem (2004) 1.40
Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol (2003) 1.38
Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1. J Biol Chem (2005) 1.36
APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. J Biol Chem (2002) 1.34
Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation. J Neurosci (2005) 1.34
Evidence for a physical interaction between presenilin and Notch. Proc Natl Acad Sci U S A (1999) 1.30
Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation. Proc Natl Acad Sci U S A (2000) 1.30
Glu-333 of nicastrin directly participates in gamma-secretase activity. J Biol Chem (2009) 1.30
Evidence that the "NF" motif in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2. J Biol Chem (2005) 1.28
Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex. J Biol Chem (2004) 1.26
Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment. Proc Natl Acad Sci U S A (2008) 1.26
Gamma-secretase complex assembly within the early secretory pathway. J Biol Chem (2004) 1.16
Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging. J Neurosci (2003) 1.14
Immature nicastrin stabilizes APH-1 independent of PEN-2 and presenilin: identification of nicastrin mutants that selectively interact with APH-1. J Neurochem (2004) 1.09
Rapid purification of active gamma-secretase, an intramembrane protease implicated in Alzheimer's disease. J Neurochem (2007) 1.05
Chemical cross-linking provides a model of the gamma-secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1. J Biol Chem (2008) 1.01
The transmembrane domain region of nicastrin mediates direct interactions with APH-1 and the gamma-secretase complex. J Biol Chem (2003) 1.00
Nicastrin is dispensable for gamma-secretase protease activity in the presence of specific presenilin mutations. J Biol Chem (2009) 0.97
Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex. J Biol Chem (2003) 0.95
APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes. J Biol Chem (2009) 0.94
Gene dosage effect on gamma-secretase component Aph-1b in a rat model for neurodevelopmental disorders. Neuron (2005) 0.93
Reduced Aph-1b expression causes tissue- and substrate-specific changes in gamma-secretase activity in rats with a complex phenotype. FASEB J (2005) 0.82
The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science (2002) 49.51
Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature (2002) 19.36
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol (2007) 17.69
Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med (2008) 17.09
Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci (2004) 9.73
A beta oligomers - a decade of discovery. J Neurochem (2007) 8.88
Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci (2007) 8.27
Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron (2009) 7.02
PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell (2011) 5.98
Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A (2003) 5.44
α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature (2011) 5.27
Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron (2004) 4.88
Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis. J Neurosci (2006) 4.14
Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron (2003) 4.11
Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers. J Physiol (2006) 3.74
Dopamine covalently modifies and functionally inactivates parkin. Nat Med (2005) 3.43
Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A (2003) 3.36
Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med (2005) 3.28
Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. Am J Pathol (2004) 3.24
Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci U S A (2011) 3.11
Functional alterations in memory networks in early Alzheimer's disease. Neuromolecular Med (2010) 2.77
Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med (2012) 2.77
Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci (2008) 2.77
Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation. J Neurosci (2005) 2.57
A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci (2007) 2.48
Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology (2013) 2.47
The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron (2003) 2.43
Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry (2009) 2.38
Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci (2011) 2.33
The presence of sodium dodecyl sulphate-stable Abeta dimers is strongly associated with Alzheimer-type dementia. Brain (2010) 2.29
The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. J Biol Chem (2003) 2.22
Purification and characterization of the human gamma-secretase complex. Biochemistry (2004) 2.18
Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration. Protein Pept Lett (2004) 2.16
Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate. Proc Natl Acad Sci U S A (2002) 2.16
Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med (2012) 2.01
Direct and potent regulation of gamma-secretase by its lipid microenvironment. J Biol Chem (2008) 2.00
Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J Biol Chem (2007) 1.95
The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J Neurochem (2011) 1.93
Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J Biol Chem (2003) 1.83
Depression is associated with low plasma Abeta42 independently of cardiovascular disease in the homebound elderly. Int J Geriatr Psychiatry (2007) 1.81
Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1. Neural Dev (2008) 1.79
Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci U S A (2006) 1.77
Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Hum Mol Genet (2007) 1.76
Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers. Neuron (2013) 1.76
Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J Mol Biol (2008) 1.75
Alzheimer's disease abeta vaccine reduces central nervous system abeta levels in a non-human primate, the Caribbean vervet. Am J Pathol (2004) 1.66
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 (2004) 1.61
Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest (2003) 1.59
Inflammation and therapeutic vaccination in CNS diseases. Nature (2002) 1.58
Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer disease. PLoS Med (2007) 1.55
Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol (2002) 1.54
Dynamic analysis of amyloid β-protein in behaving mice reveals opposing changes in ISF versus parenchymal Aβ during age-related plaque formation. J Neurosci (2011) 1.53
Identification of beta-secretase (BACE1) substrates using quantitative proteomics. PLoS One (2009) 1.52
Intraneuronal Abeta42 accumulation in Down syndrome brain. Amyloid (2002) 1.52
Gamma-secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage. J Biol Chem (2004) 1.49
Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers. Ann Neurol (2006) 1.48
Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biol (2008) 1.45
gamma-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site. J Biol Chem (2005) 1.45
A seed for Alzheimer amyloid in the brain. J Neurosci (2004) 1.45
A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease. Arch Neurol (2009) 1.44
Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J Biol Chem (2005) 1.44
Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria. Biochem J (2004) 1.43
Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s). Biochemistry (2003) 1.42
Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies. Arch Neurol (2011) 1.42
Kinetics of amyloid beta-protein degradation determined by novel fluorescence- and fluorescence polarization-based assays. J Biol Chem (2003) 1.42
Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis. Arch Neurol (2012) 1.37
Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol Dis (2009) 1.37
Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy. Am J Pathol (2007) 1.36
Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm (Vienna) (2011) 1.35
Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin. PLoS One (2010) 1.35
Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation. J Neurosci (2005) 1.34
Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice. Neurobiol Dis (2003) 1.32
Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic (2008) 1.30
Biochemical and functional interaction of disrupted-in-schizophrenia 1 and amyloid precursor protein regulates neuronal migration during mammalian cortical development. J Neurosci (2010) 1.29
Alternative splicing of human insulin-degrading enzyme yields a novel isoform with a decreased ability to degrade insulin and amyloid beta-protein. Biochemistry (2005) 1.26
Aggregation and catabolism of disease-associated intra-Abeta mutations: reduced proteolysis of AbetaA21G by neprilysin. Neurobiol Dis (2008) 1.23
Inhibition of receptor-mediated endocytosis demonstrates generation of amyloid beta-protein at the cell surface. J Biol Chem (2003) 1.22
gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins. Biochemistry (2003) 1.22
Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families. J Biol Chem (2007) 1.22
Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release. Hum Mol Genet (2009) 1.22
New ELISAs with high specificity for soluble oligomers of amyloid β-protein detect natural Aβ oligomers in human brain but not CSF. Alzheimers Dement (2013) 1.22
Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo. Eur J Neurosci (2004) 1.19
Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol (2011) 1.17
LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-beta peptide in a blood-brain barrier in vitro model. Neurobiol Dis (2008) 1.15