Structural and Chemical Biology of Presenilin Complexes

Acute Effect on the Aβ Isoform Pattern in CSF in Response to γ-Secretase Modulator and Inhibitor Treatment in Dogs

(2017) Erik Portelius et al.   JOURNAL OF ALZHEIMERS DISEASE

Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aβ Pool

(2016) Ragna Sannerud et al.   CELL

Minimization of drug–drug interaction risk and candidate selection in a natural product-based class of gamma-secretase modulators

(2015) Jed L. Hubbs et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The topology of pen-2, a γ-secretase subunit, revisited: evidence for a reentrant loop and a single pass transmembrane domain

(2015) Xulun Zhang et al.   Molecular Neurodegeneration

Amyloid-PET predicts inhibition of de novo plaque formation upon chronic γ-secretase modulator treatment

(2015) M Brendel et al.   MOLECULAR PSYCHIATRY

An atomic structure of human γ-secretase

(2015) Xiao-chen Bai et al.   NATURE

Presenilin-1 Knockin Mice Reveal Loss-of-Function Mechanism for Familial Alzheimer’s Disease

(2015) Dan Xia et al.   NEURON

Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability

(2015) Martin Pettersson et al.   ACS Medicinal Chemistry Letters

Sampling the conformational space of the catalytic subunit of human γ-secretase

(2015) Xiao-chen Bai et al.   eLife

Pen-2 Is Essential for γ-Secretase Complex Stability and Trafficking but Partially Dispensable for Endoproteolysis

(2014) Oliver Holmes et al.   BIOCHEMISTRY

Lessons from a Failed γ-Secretase Alzheimer Trial

(2014) Bart De Strooper   CELL

The dynamic conformational landscape of  -secretase

(2014) N. Elad et al.   JOURNAL OF CELL SCIENCE

Design, Synthesis, and Pharmacological Evaluation of a Novel Series of Pyridopyrazine-1,6-dione γ-Secretase Modulators

(2014) Martin Pettersson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Three-dimensional structure of human γ-secretase

(2014) Peilong Lu et al.   NATURE

Therapeutic modulation of Notch signalling — are we there yet?

(2014) Emma R. Andersson et al.   NATURE REVIEWS DRUG DISCOVERY

Allosteric regulation of  -secretase activity by a phenylimidazole-type  -secretase modulator

(2014) K. Takeo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Crystal structure of the γ-secretase component nicastrin

(2014) Tian Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Nontranscriptional Role of Hif-1α in Activation of γ-Secretase and Notch Signaling in Breast Cancer

(2014) Jennifer C. Villa et al.   Cell Reports

Development and Mechanism of γ-Secretase Modulators for Alzheimer’s Disease

(2013) Christina J. Crump et al.   BIOCHEMISTRY

Toward the structure of presenilin/γ-secretase and presenilin homologs

(2013) Michael S. Wolfe   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators

(2013) Daniel Oehlrich et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel γ-secretase modulators for the treatment of Alzheimer's disease: a review focusing on patents from 2010 to 2012

(2013) Martin Pettersson et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

γ-Secretase Modulator (GSM) Photoaffinity Probes Reveal Distinct Allosteric Binding Sites on Presenilin

(2013) Nikolay Pozdnyakov et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel γ-secretase modulator, E2212, in healthy human subjects

(2013) Yanke Yu et al.   JOURNAL OF CLINICAL PHARMACOLOGY

A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease

(2013) Rachelle S. Doody et al.   NEW ENGLAND JOURNAL OF MEDICINE

Synthesis of Pyridopyrazine-1,6-diones from 6-Hydroxypicolinic Acids via a One-Pot Coupling/Cyclization Reaction

(2013) Tuan P. Tran et al.   ORGANIC LETTERS

Structural Interactions between Inhibitor and Substrate Docking Sites Give Insight into Mechanisms of Human PS1 Complexes

(2013) Yi Li et al.   STRUCTURE

E2012-Induced Cataract and Its Predictive Biomarkers

(2013) K. Nakano-Ito et al.   TOXICOLOGICAL SCIENCES

Investigating γ-secretase protein interactions in live cells using active site-directed clickable dual-photoaffinity probes

(2013) T. Eric Ballard et al.   MedChemComm

Development of CBAP-BPyne, a probe for γ-secretase and presenilinase

(2013) Natalya Gertsik et al.   MedChemComm

Efficacy of SPI-1865, a novel gamma-secretase modulator, in multiple rodent models

(2013) Robyn M Loureiro et al.   Alzheimers Research & Therapy

Discovery of a Novel Pharmacological and Structural Class of Gamma Secretase Modulators Derived from the Extract of Actaea racemosa

(2012) Mark A. Findeis et al.   ACS Chemical Neuroscience

Pharmacokinetics and Pharmacodynamics of CHF5074 After Short-term Administration in Healthy Subjects

(2012) Bruno P. Imbimbo et al.   ALZHEIMER DISEASE & ASSOCIATED DISORDERS

Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease

(2012) Steven L. Wagner et al.   ARCHIVES OF NEUROLOGY

Safety and Tolerability of the γ-Secretase Inhibitor Avagacestat in a Phase 2 Study of Mild to Moderate Alzheimer Disease

(2012) Vladimir Coric et al.   ARCHIVES OF NEUROLOGY

BMS-708,163 Targets Presenilin and Lacks Notch-Sparing Activity

(2012) Christina J. Crump et al.   BIOCHEMISTRY

Development of clickable active site-directed photoaffinity probes for γ-secretase

(2012) Christina J. Crump et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The mechanism of γ-Secretase dysfunction in familial Alzheimer disease

(2012) Lucía Chávez-Gutiérrez et al.   EMBO JOURNAL

Familial Alzheimer Disease Presenilin-1 Mutations Alter the Active Site Conformation of γ-secretase

(2012) De-Ming Chau et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

First and Second Generation γ-Secretase Modulators (GSMs) Modulate Amyloid-β (Aβ) Peptide Production through Different Mechanisms

(2012) Tomas Borgegard et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Moving Forward One Notch at a Time

(2012) Mrinal M. Gounder et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors

(2012) Ian Krop et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I Study of RO4929097, a Gamma Secretase Inhibitor of Notch Signaling, in Patients With Refractory Metastatic or Locally Advanced Solid Tumors

(2012) Anthony W. Tolcher et al.   JOURNAL OF CLINICAL ONCOLOGY

Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators

(2012) Francois Bischoff et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of a Natural Product-Based Class of γ-Secretase Modulators

(2012) Jed L. Hubbs et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment

(2012) Guozhang Mao et al.   JOURNAL OF NEUROCHEMISTRY

Differential Effects between  -Secretase Inhibitors and Modulators on Cognitive Function in Amyloid Precursor Protein-Transgenic and Nontransgenic Mice

(2012) Y. Mitani et al.   JOURNAL OF NEUROSCIENCE

Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice

(2012) Kathryn Rogers et al.   Molecular Neurodegeneration

Structure of a presenilin family intramembrane aspartate protease

(2012) Xiaochun Li et al.   NATURE

Vigilin interacts with signal peptide peptidase

(2012) Stephen Hsueh-Jeng Lu et al.   Proteome Science

Synthesis and SAR Studies of Fused Oxadiazines as γ-Secretase Modulators for Treatment of Alzheimer's Disease

(2012) Xianhai Huang et al.   ACS Medicinal Chemistry Letters

Piperidine Acetic Acid Based γ-Secretase Modulators Directly Bind to Presenilin-1

(2011) Christina J. Crump et al.   ACS Chemical Neuroscience

Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease

(2011) B Van Broeck et al.   BRITISH JOURNAL OF PHARMACOLOGY

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

(2011) Grazia D'Onofrio et al.   Expert Opinion on Drug Discovery

Novel γ-secretase modulators: a review of patents from 2008 to 2010

(2011) Martin Pettersson et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Structure of γ-Secretase and Its Trimeric Pre-activation Intermediate by Single-particle Electron Microscopy

(2011) Fabiana Renzi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Novel γ-Secretase Enzyme Modulators Directly Target Presenilin Protein

(2011) Amelie Ebke et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo

(2011) Zhong-Yue Sun et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator

(2011) Hairuo Peng et al.   ACS Medicinal Chemistry Letters

E2012, a novel gamma-secretase modulator, decreases plasma amyloid-beta (Aβ) levels in humans

(2010) Christa Nagy et al.   Alzheimers & Dementia

E2012: A novel gamma-secretase modulator-pharmacology part

(2010) Toshihide Hashimoto et al.   Alzheimers & Dementia

Novel Research Horizons for Presenilins and γ-Secretases in Cell Biology and Disease

(2010) Bart De Strooper et al.   Annual Review of Cell and Developmental Biology

β-Amyloid Precursor Protein Mutants Respond to γ-Secretase Modulators

(2010) Richard M. Page et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Functional Analysis of the Transmembrane Domains of Presenilin 1

(2010) Naoto Watanabe et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

 -Secretase Composed of PS1/Pen2/Aph1a Can Cleave Notch and Amyloid Precursor Protein in the Absence of Nicastrin

(2010) G. Zhao et al.   JOURNAL OF NEUROSCIENCE

An APP inhibitory domain containing the Flemish mutation residue modulates γ-secretase activity for Aβ production

(2010) Yuan Tian et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Modulation of γ-Secretase Reduces β-Amyloid Deposition in a Transgenic Mouse Model of Alzheimer's Disease

(2010) Maria Z. Kounnas et al.   NEURON

Structural investigation of the C-terminal catalytic fragment of presenilin 1

(2010) S. Sobhanifar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activation and intrinsic  -secretase activity of presenilin 1

(2010) K. Ahn et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2010) Kevin W. Gillman et al.   ACS Medicinal Chemistry Letters

APH1 Polar Transmembrane Residues Regulate the Assembly and Activity of Presenilin Complexes

(2009) Raphaëlle Pardossi-Piquard et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Intramembrane Proteolysis by Signal Peptide Peptidases: A Comparative Discussion of GXGD-type Aspartyl Proteases

(2009) Regina Fluhrer et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Affinity pulldown of γ-secretase and associated proteins from human and rat brain

(2009) Yasuhiro Teranishi et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Modulation of  -secretase specificity using small molecule allosteric inhibitors

(2009) C. C. Shelton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

 -Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer's Disease

(2009) L. Serneels et al.   SCIENCE

Stereo-controlled synthesis of novel photoreactive γ-secretase inhibitors

(2008) Guangli Yang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pen2 and Presenilin-1 Modulate the Dynamic Equilibrium of Presenilin-1 and Presenilin-2 γ-Secretase Complexes

(2008) Lisa Placanica et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Intramembrane Proteolysis by γ-Secretase

(2008) Harald Steiner et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cryoelectron Microscopy Structure of Purified γ-Secretase at 12 Å Resolution

(2008) Pamela Osenkowski et al.   JOURNAL OF MOLECULAR BIOLOGY