Reconstitution of gamma-secretase activity.

PubWeight™: 4.66‹?› | Rank: Top 1%

🔗 View Article (PMID 12679784)

Published in Nat Cell Biol on May 01, 2003

Authors

Dieter Edbauer1, Edith Winkler, Joerg T Regula, Brigitte Pesold, Harald Steiner, Christian Haass

Author Affiliations

1: Adolf-Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany.

Articles citing this

(truncated to the top 100)

Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease. J Cell Biol (2005) 4.91

Alzheimer's disease: the challenge of the second century. Sci Transl Med (2011) 4.88

Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A (2006) 3.98

NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest (2003) 3.50

The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol (2010) 3.32

100 years and counting: prospects for defeating Alzheimer's disease. Science (2006) 3.24

Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis. Neuron (2006) 2.76

Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation. EMBO J (2004) 2.72

GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. EMBO J (2007) 2.61

Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med (2012) 2.56

Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron (2008) 2.40

Substrate specificity of gamma-secretase and other intramembrane proteases. Cell Mol Life Sci (2008) 2.29

Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol (2007) 2.09

Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc Natl Acad Sci U S A (2005) 2.08

APP processing in Alzheimer's disease. Mol Brain (2011) 2.02

Presenilins and γ-secretase: structure, function, and role in Alzheimer Disease. Cold Spring Harb Perspect Med (2012) 2.02

The many substrates of presenilin/γ-secretase. J Alzheimers Dis (2011) 2.02

SORCS1 alters amyloid precursor protein processing and variants may increase Alzheimer's disease risk. Ann Neurol (2011) 2.01

Direct and potent regulation of gamma-secretase by its lipid microenvironment. J Biol Chem (2008) 2.00

The amyloid precursor protein: beyond amyloid. Mol Neurodegener (2006) 1.98

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

When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep (2007) 1.81

Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J Mol Biol (2008) 1.75

Intramembrane proteolysis by gamma-secretase. J Biol Chem (2008) 1.74

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

Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. Proc Natl Acad Sci U S A (2005) 1.69

Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol (2010) 1.68

Activation and intrinsic gamma-secretase activity of presenilin 1. Proc Natl Acad Sci U S A (2010) 1.62

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

Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron (2008) 1.59

Biology and pathophysiology of the amyloid precursor protein. Mol Neurodegener (2011) 1.58

Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc Natl Acad Sci U S A (2007) 1.56

Inhibition and modulation of gamma-secretase for Alzheimer's disease. Neurotherapeutics (2008) 1.55

LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease. Proc Natl Acad Sci U S A (2006) 1.50

Dscam guides embryonic axons by Netrin-dependent and -independent functions. Development (2008) 1.50

Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Proc Natl Acad Sci U S A (2006) 1.41

Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol (2003) 1.38

Pathological and physiological functions of presenilins. Mol Neurodegener (2006) 1.38

Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem (2005) 1.37

Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis (2010) 1.33

Intramembrane proteolysis. Chem Rev (2009) 1.32

Dissociation between the processivity and total activity of γ-secretase: implications for the mechanism of Alzheimer's disease-causing presenilin mutations. Biochemistry (2011) 1.30

Glu-333 of nicastrin directly participates in gamma-secretase activity. J Biol Chem (2009) 1.30

Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci (2008) 1.30

Hydrogen peroxide promotes Abeta production through JNK-dependent activation of gamma-secretase. J Biol Chem (2008) 1.27

The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity. EMBO J (2004) 1.26

Taking the plunge: integrating structural, enzymatic and computational insights into a unified model for membrane-immersed rhomboid proteolysis. Biochem J (2010) 1.25

Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease. Curr Alzheimer Res (2008) 1.25

Induced dimerization of the amyloid precursor protein leads to decreased amyloid-beta protein production. J Biol Chem (2009) 1.25

Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains. Nat Cell Biol (2009) 1.25

An AICD-based functional screen to identify APP metabolism regulators. Mol Neurodegener (2007) 1.22

Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci (2010) 1.21

Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexes. J Biol Chem (2008) 1.20

Intramembrane proteolysis by signal peptide peptidases: a comparative discussion of GXGD-type aspartyl proteases. J Biol Chem (2009) 1.20

The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system. EMBO Mol Med (2009) 1.20

NOTCHing the bone: insights into multi-functionality. Bone (2009) 1.19

Mouse models of Alzheimer's disease. Brain Res Bull (2011) 1.19

Development and mechanism of γ-secretase modulators for Alzheimer's disease. Biochemistry (2013) 1.18

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

Crystal structure of the γ-secretase component nicastrin. Proc Natl Acad Sci U S A (2014) 1.13

Beta-amyloid precursor protein mutants respond to gamma-secretase modulators. J Biol Chem (2010) 1.12

Small molecule blockers of the Alzheimer Abeta calcium channel potently protect neurons from Abeta cytotoxicity. Proc Natl Acad Sci U S A (2009) 1.12

Gamma-secretase inhibition and modulation for Alzheimer's disease. Curr Alzheimer Res (2008) 1.09

Membrane binding properties and terminal residues of the mature hepatitis C virus capsid protein in insect cells. J Virol (2004) 1.08

Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta. J Biol Chem (2008) 1.07

Toward structural elucidation of the gamma-secretase complex. Structure (2009) 1.07

Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy. J Biol Chem (2011) 1.06

Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of γ-secretase using synthetic antibodies. Proc Natl Acad Sci U S A (2012) 1.06

Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer's disease. Front Physiol (2012) 1.05

Mutagenesis mapping of the presenilin 1 calcium leak conductance pore. J Biol Chem (2011) 1.05

Targets for AD treatment: conflicting messages from γ-secretase inhibitors. J Neurochem (2011) 1.05

Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates. Mol Neurodegener (2006) 1.05

Neuronal protein trafficking associated with Alzheimer disease: from APP and BACE1 to glutamate receptors. Cell Adh Migr (2009) 1.05

Phorbol 12-myristate 13-acetate-induced release of the colony-stimulating factor 1 receptor cytoplasmic domain into the cytosol involves two separate cleavage events. Mol Cell Biol (2004) 1.04

Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases. Curr Opin Struct Biol (2008) 1.04

Effects of membrane lipids on the activity and processivity of purified γ-secretase. Biochemistry (2012) 1.03

Disease-modifying treatments for Alzheimer's disease. Ther Adv Neurol Disord (2011) 1.03

Dictyostelium possesses highly diverged presenilin/gamma-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/gamma-secretase complex. Dis Model Mech (2010) 1.02

Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation. Traffic (2011) 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

Truncated and modified amyloid-beta species. Alzheimers Res Ther (2014) 1.01

The presenilin-1 ΔE9 mutation results in reduced γ-secretase activity, but not total loss of PS1 function, in isogenic human stem cells. Cell Rep (2013) 1.00

In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells. Biol Chem (2008) 0.99

Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. Am J Pathol (2009) 0.99

Recent rodent models for Alzheimer's disease: clinical implications and basic research. J Neural Transm (Vienna) (2011) 0.99

Complex regulation of γ-secretase: from obligatory to modulatory subunits. Front Aging Neurosci (2015) 0.99

Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis. Cell Calcium (2011) 0.99

Nicastrin functions to sterically hinder γ-secretase-substrate interactions driven by substrate transmembrane domain. Proc Natl Acad Sci U S A (2015) 0.98

Soluble γ-secretase modulators selectively inhibit the production of the 42-amino acid amyloid β peptide variant and augment the production of multiple carboxy-truncated amyloid β species. Biochemistry (2014) 0.98

Nicastrin is dispensable for gamma-secretase protease activity in the presence of specific presenilin mutations. J Biol Chem (2009) 0.97

Nicalin and its binding partner Nomo are novel Nodal signaling antagonists. EMBO J (2004) 0.96

Allosteric regulation of rhomboid intramembrane proteolysis. EMBO J (2014) 0.96

Proteolytic cleavage of Notch: "HIT and RUN". Curr Mol Med (2011) 0.95

Signature amyloid β profiles are produced by different γ-secretase complexes. J Biol Chem (2013) 0.94

Nontranscriptional role of Hif-1α in activation of γ-secretase and notch signaling in breast cancer. Cell Rep (2014) 0.94

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

APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes. J Biol Chem (2009) 0.94

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease. Front Aging Neurosci (2013) 0.94

Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein. Mol Brain (2008) 0.94

Articles by these authors

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

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

Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis. Neuron (2008) 2.99

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

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

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

PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin. J Biol Chem (2002) 1.71

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

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

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

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

Identification of distinct gamma-secretase complexes with different APH-1 variants. J Biol Chem (2004) 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

TDP-43 and FUS: a nuclear affair. Trends Neurosci (2011) 1.35

Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway. J Neurosci (2009) 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

Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases. Trends Cell Biol (2002) 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

Assembly, trafficking and function of gamma-secretase. Neurodegener Dis (2006) 1.22

Stress granules in neurodegeneration--lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J (2013) 1.21

Intramembrane proteolysis by signal peptide peptidases: a comparative discussion of GXGD-type aspartyl proteases. J Biol Chem (2009) 1.20

The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system. EMBO Mol Med (2009) 1.20