Advances in the identification of γ-secretase inhibitors for the treatment of Alzheimer's disease. (Q37999086)

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27 January 2020

title

Advances in the identification of γ-secretase inhibitors for the treatment of Alzheimer's disease (English)

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27 January 2020

1

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27 January 2020

Francesco Panza

2

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27 January 2020

Vincenza Frisardi

3

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27 January 2020

Bruno Imbimbo

5

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27 January 2020

Giulia Paroni

6

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27 January 2020

4

Vincenzo Solfrizzi

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27 January 2020

8

Davide Seripa

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27 January 2020

author name string

Leandro Cascavilla

7

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27 January 2020

Alberto Pilotto

9

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27 January 2020

language of work or name

English

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publication date

14 December 2011

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Expert Opinion on Drug Discovery

27 January 2020

published in

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27 January 2020

volume

7

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27 January 2020

page(s)

19-37

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27 January 2020

issue

1

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2011 Alzheimer's disease facts and figures

27 January 2020

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Secretase inhibitors and modulators for Alzheimer's disease treatment

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gamma-Secretase as a therapeutic target in Alzheimer's disease

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γ-secretase substrates and their implications for drug development in Alzheimer's disease

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

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Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing

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Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms

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REVIEW: γ-Secretase inhibitors for the treatment of Alzheimer's disease: The current state.

21 January 2018

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Activity of gamma-secretase on substrates other than APP.

21 January 2018

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

21 January 2018

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A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity

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The non-cyclooxygenase targets of non-steroidal anti-inflammatory drugs, lipoxygenases, peroxisome proliferator-activated receptor, inhibitor of kappa B kinase, and NF kappa B, do not reduce amyloid beta 42 production

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NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo

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Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation

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Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production

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

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Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease

21 January 2018

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

21 January 2018

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

21 January 2018

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Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation

21 January 2018

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Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity

21 January 2018

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Nicastrin functions as a gamma-secretase-substrate receptor

21 January 2018

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aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation

21 January 2018

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Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions.

21 January 2018

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gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease

21 January 2018

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Identification of distinct gamma-secretase complexes with different APH-1 variants

21 January 2018

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Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity

21 January 2018

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APH-1a is the principal mammalian APH-1 isoform present in gamma-secretase complexes during embryonic development

21 January 2018

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Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo

21 January 2018

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Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities

21 January 2018

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Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment

21 January 2018

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Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes

21 January 2018

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Membrane topology of gamma-secretase component PEN-2.

21 January 2018

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Functional and topological analysis of Pen-2, the fourth subunit of the gamma-secretase complex

21 January 2018

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

21 January 2018

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Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex

21 January 2018

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A sequence within the first transmembrane domain of PEN-2 is critical for PEN-2-mediated endoproteolysis of presenilin 1.

21 January 2018

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Active gamma-secretase complexes contain only one of each component

21 January 2018

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Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores

21 January 2018

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Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution

21 January 2018

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A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain

21 January 2018

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A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations

21 January 2018

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gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase

21 January 2018

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The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease

21 January 2018

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Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation

21 January 2018

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Notch signaling, gamma-secretase inhibitors, and cancer therapy

21 January 2018

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Catalytic site-directed gamma-secretase complex inhibitors do not discriminate pharmacologically between Notch S3 and beta-APP cleavages

21 January 2018

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Direct regulation of intestinal fate by Notch

21 January 2018

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Emerging role of Notch signaling in epidermal differentiation and skin cancer

21 January 2018

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

21 January 2018

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Notch: from neural development to neurological disorders

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Learning and memory deficits in Notch mutant mice.

21 January 2018

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Involvement of Notch signaling in hippocampal synaptic plasticity

21 January 2018

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Recent progress in the medicinal chemistry of gamma-secretase inhibitors

21 January 2018

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

21 January 2018

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

21 January 2018

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Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease.

21 January 2018

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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

21 January 2018

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Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibition

21 January 2018

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Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575.

21 January 2018

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Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139.

21 January 2018

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Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway.

21 January 2018

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Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta after inhibition of gamma-secretase

21 January 2018

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

21 January 2018

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

21 January 2018

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Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease

21 January 2018

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A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system

21 January 2018

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Are γ-secretase inhibitors detrimental for Alzheimer's disease patients?

21 January 2018

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Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease

21 January 2018

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Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor

21 January 2018

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Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.

21 January 2018

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Current concepts in Alzheimer's disease: a multidisciplinary review

21 January 2018

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Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity

21 January 2018

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The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons

21 January 2018

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p53 is regulated by and regulates members of the gamma-secretase complex

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

In vivo inhibition of Abeta production by memapsin 2 (beta-secretase) inhibitors

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Abeta40 inhibits amyloid deposition in vivo.

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Is brain amyloid production a cause or a result of dementia of the Alzheimer's type?

21 January 2018

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https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Tau reduction prevents Abeta-induced defects in axonal transport.

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

The Alzheimer's disease neuroimaging initiative: progress report and future plans

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534

Three-dimensional structure of the γ-secretase complex

21 January 2018

1 reference

https://api.crossref.org/works/10.1517%2F17460441.2012.645534