Published in J Biol Chem on August 26, 2002
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
Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem (2004) 2.85
Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set. Physiol Genomics (2008) 2.11
The many substrates of presenilin/γ-secretase. J Alzheimers Dis (2011) 2.02
A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci U S A (2003) 1.92
CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production. Proc Natl Acad Sci U S A (2005) 1.73
Proteolytic processing of Alzheimer's β-amyloid precursor protein. J Neurochem (2011) 1.50
The ubiquitin-proteasome system in Alzheimer's disease. J Cell Mol Med (2008) 1.46
Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol (2003) 1.38
Anesthetic sevoflurane causes neurotoxicity differently in neonatal naïve and Alzheimer disease transgenic mice. Anesthesiology (2010) 1.38
Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem (2005) 1.37
Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS One (2009) 1.34
The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions. J Biol Chem (2008) 1.31
Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region. EMBO Rep (2004) 1.27
The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity. EMBO J (2004) 1.26
Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease. Curr Alzheimer Res (2008) 1.25
Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration. J Neurosci (2009) 1.23
Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin. Biochem J (2005) 1.14
Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. J Cell Mol Med (2007) 1.13
Trans-dominant negative effects of pathogenic PSEN1 mutations on γ-secretase activity and Aβ production. J Neurosci (2013) 1.08
Attenuated Abeta42 responses to low potency gamma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds. J Biol Chem (2011) 1.05
Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells. J Neuroinflammation (2012) 1.03
Transcriptional regulation of PEN-2, a key component of the gamma-secretase complex, by CREB. Mol Cell Biol (2006) 1.02
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
γ-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1. J Biol Chem (2011) 0.98
Functional and topological analysis of Pen-2, the fourth subunit of the gamma-secretase complex. J Biol Chem (2011) 0.97
Nicalin and its binding partner Nomo are novel Nodal signaling antagonists. EMBO J (2004) 0.96
Characterization of an atypical gamma-secretase complex from hematopoietic origin. Biochemistry (2010) 0.95
Generation of Alzheimer disease-associated amyloid β42/43 peptide by γ-secretase can be inhibited directly by modulation of membrane thickness. J Biol Chem (2012) 0.94
Genetics of Alzheimer's disease. Biomed Res Int (2013) 0.90
General anesthetics and β-amyloid protein. Prog Neuropsychopharmacol Biol Psychiatry (2012) 0.89
The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid. Neurochem Res (2006) 0.87
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
Structural and Functional Determinants of gamma-Secretase, an Intramembrane Protease Implicated in Alzheimer's Disease. Curr Genomics (2007) 0.84
The endocannabinoid, anandamide, augments Notch-1 signaling in cultured cortical neurons exposed to amyloid-β and in the cortex of aged rats. J Biol Chem (2012) 0.83
Small molecules intercept Notch signaling and the early secretory pathway. Nat Chem Biol (2013) 0.83
Mutations in nicastrin protein differentially affect amyloid beta-peptide production and Notch protein processing. J Biol Chem (2011) 0.82
Transcriptional Regulation of TMP21 by NFAT. Mol Neurodegener (2011) 0.82
Inferring combinatorial association logic networks in multimodal genome-wide screens. Bioinformatics (2010) 0.82
Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment. J Neurochem (2012) 0.82
Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice. Neurobiol Aging (2014) 0.81
The γ-secretase complex: from structure to function. Front Cell Neurosci (2014) 0.81
Γ-secretase components as predictors of breast cancer outcome. PLoS One (2013) 0.80
Increased expression of PS1 is sufficient to elevate the level and activity of γ-secretase in vivo. PLoS One (2011) 0.79
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
Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins. Biochem J (2006) 0.77
The topology of pen-2, a γ-secretase subunit, revisited: evidence for a reentrant loop and a single pass transmembrane domain. Mol Neurodegener (2015) 0.76
Overexpression of N141I PS2 increases γ-secretase activity through up-regulation of Presenilin and Pen-2 in brain mitochondria of NSE/hPS2m transgenic mice. Lab Anim Res (2016) 0.75
The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science (2013) 6.34
Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci (2007) 5.68
Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol (2003) 4.71
Reconstitution of gamma-secretase activity. Nat Cell Biol (2003) 4.66
Control of peripheral nerve myelination by the beta-secretase BACE1. Science (2006) 4.55
Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep (2006) 4.06
Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science (2008) 3.59
ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J (2010) 3.58
A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep (2002) 3.53
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med (2012) 3.49
Different species of alpha-synuclein oligomers induce calcium influx and seeding. J Neurosci (2007) 3.16
Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis. Neuron (2008) 2.99
Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Nat Neurosci (2009) 2.85
Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci (2010) 2.79
Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem (2009) 2.64
Role of Septin cytoskeleton in spine morphogenesis and dendrite development in neurons. Curr Biol (2007) 2.60
Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest (2002) 2.47
microRNA-34c is a novel target to treat dementias. EMBO J (2011) 2.44
The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J (2008) 2.43
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. EMBO J (2012) 2.36
Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci U S A (2002) 2.29
hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta Neuropathol (2013) 2.27
Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. Development (2013) 2.22
Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J (2010) 2.12
The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. J Biol Chem (2003) 1.99
Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. J Biol Chem (2002) 1.97
Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep (2002) 1.91
Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion. J Biol Chem (2007) 1.87
Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol (2013) 1.82
Regulated intramembrane proteolysis--lessons from amyloid precursor protein processing. J Neurochem (2011) 1.79
Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta (2009) 1.77
Reactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog. [corrected]. Cell Stem Cell (2013) 1.77
Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. J Neurochem (2009) 1.76
FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations. Brain (2011) 1.76
Intramembrane proteolysis by gamma-secretase. J Biol Chem (2008) 1.74
Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics study. J Biol Chem (2004) 1.73
Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. J Biol Chem (2007) 1.71
Active gamma-secretase complexes contain only one of each component. J Biol Chem (2007) 1.69
Distinct roles of NR2A and NR2B cytoplasmic tails in long-term potentiation. J Neurosci (2010) 1.65
Games played by rogue proteins in prion disorders and Alzheimer's disease. Science (2003) 1.61
Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J (2012) 1.61
Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta Neuropathol (2013) 1.59
Boxing-acute complications and late sequelae: from concussion to dementia. Dtsch Arztebl Int (2010) 1.59
Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Traffic (2006) 1.57
Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1. EMBO J (2002) 1.57
How does parkin ligate ubiquitin to Parkinson's disease? EMBO Rep (2004) 1.54
Potential link between amyloid beta-protein 42 and C-terminal fragment gamma 49-99 of beta-amyloid precursor protein. J Biol Chem (2003) 1.49
MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proc Natl Acad Sci U S A (2012) 1.49
Functional impairment of microglia coincides with Beta-amyloid deposition in mice with Alzheimer-like pathology. PLoS One (2013) 1.48
C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol (2014) 1.48
GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network. Mol Cell Neurosci (2005) 1.47
Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. J Biol Chem (2007) 1.46
Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD). J Biol Chem (2002) 1.45
Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J (2012) 1.45
Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1. J Biol Chem (2003) 1.45
Secretion of the Notch-1 Abeta-like peptide during Notch signaling. J Biol Chem (2006) 1.44
Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation. Proc Natl Acad Sci U S A (2002) 1.44
Requirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43). J Biol Chem (2012) 1.43
Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane. J Cell Biol (2002) 1.42
Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chem Biol (2009) 1.42
Identification of distinct gamma-secretase complexes with different APH-1 variants. J Biol Chem (2004) 1.40
Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase. J Neurochem (2013) 1.40
miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nat Neurosci (2011) 1.40
The N-terminus of the intrinsically disordered protein α-synuclein triggers membrane binding and helix folding. Biophys J (2010) 1.39
Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem (2014) 1.37
Membrane orientation and subcellular localization of transmembrane protein 106B (TMEM106B), a major risk factor for frontotemporal lobar degeneration. J Biol Chem (2012) 1.37
Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol (2005) 1.36
A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b. Nat Cell Biol (2006) 1.36
Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway. J Neurosci (2009) 1.35
TDP-43 and FUS: a nuclear affair. Trends Neurosci (2011) 1.35
Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin's transcriptional activity. Mol Cell Biol (2006) 1.32
A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest (2009) 1.32
Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem (2004) 1.28
Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region. EMBO Rep (2004) 1.27
Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta-, and gamma-secretase. J Biol Chem (2007) 1.27
The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity. EMBO J (2004) 1.26
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
Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice. Neurobiol Aging (2006) 1.26
Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. J Neurosci (2011) 1.26
Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes. Neurobiol Dis (2007) 1.25
Novel γ-secretase enzyme modulators directly target presenilin protein. J Biol Chem (2011) 1.24
Early dipeptide repeat pathology in a frontotemporal dementia kindred with C9ORF72 mutation and intellectual disability. Acta Neuropathol (2014) 1.24
Assembly, trafficking and function of gamma-secretase. Neurodegener Dis (2006) 1.22