(Q37130650)

18 August 2017

1 reference

title

Gamma-secretase inhibition and modulation for Alzheimer's disease (English)

1 reference

18 August 2017

0 references

Michael S Wolfe

1

1 reference

18 August 2017

1 April 2008

1 reference

Current Alzheimer Research

18 August 2017

1 reference

18 August 2017

5

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18 August 2017

2

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18 August 2017

158-164

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The gamma-secretase complex: membrane-embedded proteolytic ensemble

18 August 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Deducing the transmembrane domain organization of presenilin-1 in gamma-secretase by cysteine disulfide cross-linking

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

gamma-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The initial substrate-binding site of gamma-secretase is located on presenilin near the active site

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism.

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Purification and characterization of the human gamma-secretase complex

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Gleevec inhibits β-amyloid production but not Notch cleavage

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Identification of a Novel Aspartic Protease (Asp 2) as β-Secretase

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Purification and cloning of amyloid precursor protein beta-secretase from human brain

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Endoproteolytic processing and stabilization of wild-type and mutant presenilin

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Secretion of the Notch-1 Abeta-like peptide during Notch signaling

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Evidence that the "NF" motif in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2.

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

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

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The role of presenilin cofactors in the gamma-secretase complex

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage

14 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

A substrate-based difluoro ketone selectively inhibits Alzheimer's gamma-secretase activity.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors.

27 June 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.

27 June 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease

27 June 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Nicastrin functions as a gamma-secretase-substrate receptor

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Quantitative measurement of changes in amyloid-beta(40) in the rat brain and cerebrospinal fluid following treatment with the gamma-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897.

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Gamma-secretase: proteasome of the membrane?

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Designed Helical Peptides Inhibit an Intramembrane Protease

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Reconstitution of gamma-secretase activity

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Amyloid-lowering isocoumarins are not direct inhibitors of gamma-secretase

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells.

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Transition-state analogue inhibitors of gamma-secretase bind directly to presenilin-1.

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Divergent Synthesis of Multifunctional Molecular Probes To Elucidate the Enzyme Specificity of Dipeptidic γ-Secretase Inhibitors

3 September 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

C-terminal Fragment of Presenilin Is the Molecular Target of a Dipeptidic γ-Secretase-specific Inhibitor DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycinet-Butyl Ester)

4 December 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=2675939

Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1

4 December 2018

1 reference

12 December 2020

Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors

1 reference

12 December 2020

Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase

1 reference

12 December 2020

Peptidomimetic probes and molecular modeling suggest that Alzheimer's gamma-secretase is an intramembrane-cleaving aspartyl protease

1 reference

12 December 2020

10.2174/156720508783954767

Identifiers

DOI

1 reference

18 August 2017

1 reference

18 August 2017

1 reference

PMCID

2675939