BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease

MONITORING THE SOLUBLE AMYLOID PRECURSOR PROTEIN ALPHA (SAPPA) AND BETA (SAPPB) FRAGMENTS IN PLASMA AND CSF FROM HEALTHY INDIVIDUALS TREATED WITH BACE INHIBITOR AZD3293 IN A MULTIPLE ASCENDING DOSE STUDY: PHARMACOKINETIC AND PHARMACODYNAMIC CORRELATE

(2014) Kina Höglund et al.   Alzheimers & Dementia

Molecular Mechanisms of Alzheimer Disease Protection by the A673T Allele of Amyloid Precursor Protein

(2014) Janice A. Maloney et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation

(2014) Iryna Benilova et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

AZD3293 A novel BACE1 inhibitor: safety, tolerability, and effects on plasma and CSF Aβ peptides following single- and multiple-dose administration

(2014) Robert Alexander et al.   NEUROBIOLOGY OF AGING

Genetic Inhibition of Phosphorylation of the Translation Initiation Factor eIF2α Does Not Block Aβ-Dependent Elevation of BACE1 and APP Levels or Reduce Amyloid Pathology in a Mouse Model of Alzheimer’s Disease

(2014) Katherine R. Sadleir et al.   PLoS One

Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates

(2014) Y. J. Yu et al.   Science Translational Medicine

The Alzheimer’s β-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques

(2013) Patty C. Kandalepas et al.   ACTA NEUROPATHOLOGICA

The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate Alzheimer's disease

(2013) Mark Forman et al.   Alzheimers & Dementia

Clinical study of E2609, a novel BACE1 inhibitor, demonstrates target engagement and inhibition of BACE1 activity in CSF

(2013) Francois Bernier et al.   Alzheimers & Dementia

Allosteric inhibition of BACE1 by an exosite-binding antibody

(2013) Weiru Wang et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles

(2013) Cyril Cheret et al.   EMBO JOURNAL

Increased Expression of Reticulon 3 in Neurons Leads to Reduced Axonal Transport of β Site Amyloid Precursor Protein-cleaving Enzyme 1

(2013) Minzi Deng et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Dual Cleavage of Neuregulin 1 Type III by BACE1 and ADAM17 Liberates Its EGF-Like Domain and Allows Paracrine Signaling

(2013) D. Fleck et al.   JOURNAL OF NEUROSCIENCE

Immunotherapy for Alzheimer’s disease: hoops and hurdles

(2013) Cynthia A Lemere   Molecular Neurodegeneration

Current concepts in Alzheimer’s Disease: molecules, models and translational perspectives

(2013) Bart PF Rutten et al.   Molecular Neurodegeneration

Fluid biomarkers in Alzheimer’s disease – current concepts

(2013) Christoffer Rosén et al.   Molecular Neurodegeneration

Cross-talk of membrane lipids and Alzheimer-related proteins

(2013) Jochen Walter et al.   Molecular Neurodegeneration

Blood–brain-barriers in aging and in Alzheimer’s disease

(2013) Fernanda Marques et al.   Molecular Neurodegeneration

Biomarker Modeling of Alzheimer’s Disease

(2013) Clifford R. Jack et al.   NEURON

Genetic and biochemical evidence for a functional role of BACE1 in the regulation of insulin mRNA expression

(2013) Albrecht Hoffmeister et al.   Obesity

BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells

(2013) L. Rochin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BACE1 Regulates Hippocampal Astrogenesis via the Jagged1-Notch Pathway

(2013) Xiangyou Hu et al.   Cell Reports

The Genetics of Alzheimer Disease

(2013) R. E. Tanzi   Cold Spring Harbor Perspectives in Medicine

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

(2013) R. Tarawneh et al.   Cold Spring Harbor Perspectives in Medicine

The novel BACE inhibitor MK-8931 dramatically lowers cerebrospinal fluid Aβ peptides in healthy subjects following single- and multiple-dose administration

(2012) Mark Forman et al.   Alzheimers & Dementia

Central BACE1 inhibition by LY2886721 produces opposing effects on APP processing as reflected by cerebrospinal fluid sAPPalpha and sAPPbeta

(2012) Brian Willis et al.   Alzheimers & Dementia

BACE inhibitor LY2886721 safety and central and peripheral PK and PD in healthy subjects (HSs)

(2012) Ferenc Martenyi et al.   Alzheimers & Dementia

First-in-human study of E2609, a novel BACE1 inhibitor, demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing

(2012) Robert Lai et al.   Alzheimers & Dementia

Origins of Alzheimerʼs disease

(2012) Erik S. Musiek et al.   CURRENT OPINION IN NEUROLOGY

Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons

(2012) Peer-Hendrik Kuhn et al.   EMBO JOURNAL

β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment

(2012) Jun Cai et al.   EMBO Molecular Medicine

Small-molecule BACE1 inhibitors: a patent literature review (2006 – 2011)

(2012) Gary Probst et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Cdk5 Protein Inhibition and Aβ42 Increase BACE1 Protein Level in Primary Neurons by a Post-transcriptional Mechanism

(2012) Katherine R. Sadleir et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

(2012) Brian Hitt et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Neural Cell Adhesion Molecules L1 and CHL1 Are Cleaved by BACE1 Proteasein Vivo

(2012) Lujia Zhou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Axonal regulation of Schwann cell ensheathment and myelination

(2012) James L. Salzer   JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM

Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing

(2012) Yonghao Zhao et al.   Molecular Neurodegeneration

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus

(2012) Manuel Torres et al.   Molecular Neurodegeneration

Identification of BACE2 as an avid ß-amyloid-degrading protease

(2012) Samer O Abdul-Hay et al.   Molecular Neurodegeneration

BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease

(2012) Linda Chami et al.   Molecular Neurodegeneration

A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline

(2012) Thorlakur Jonsson et al.   NATURE

Beneficial Effect of Antibodies against β- Secretase Cleavage Site of App on Alzheimer’s-Like Pathology in Triple-Transgenic Mice

(2012) Inna Rabinovich-Nikitin et al.   PLoS One

Alzheimer Disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play

(2012) Clifford R. Jack   RADIOLOGY

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

(2011) Paul J. Meakin et al.   BIOCHEMICAL JOURNAL

Bace2 Is a β Cell-Enriched Protease that Regulates Pancreatic β Cell Function and Mass

(2011) Daria Esterházy et al.   Cell Metabolism

Inhibition of β-Secretasein Vivovia Antibody Binding to Unique Loops (D and F) of BACE1

(2011) Lujia Zhou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cleavage of Neuregulin-1 by BACE1 or ADAM10 Protein Produces Differential Effects on Myelination

(2011) Xiaoyang Luo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Robust Central Reduction of Amyloid-  in Humans with an Orally Available, Non-Peptidic  -Secretase Inhibitor

(2011) P. C. May et al.   JOURNAL OF NEUROSCIENCE

The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb

(2011) Tharinda W Rajapaksha et al.   Molecular Neurodegeneration

A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-  Production in Vivo

(2011) J. K. Atwal et al.   Science Translational Medicine

Inhibiting β-Secretase Activity in Alzheimer's Disease Cell Models with Single-Chain Antibodies Specifically Targeting APP

(2010) Shanta Boddapati et al.   JOURNAL OF MOLECULAR BIOLOGY

BACE1 Deficiency Causes Altered Neuronal Activity and Neurodegeneration

(2010) X. Hu et al.   JOURNAL OF NEUROSCIENCE

BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization

(2010) Brian D. Hitt et al.   Molecular Neurodegeneration

The secretases: enzymes with therapeutic potential in Alzheimer disease

(2010) Bart De Strooper et al.   Nature Reviews Neurology

The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism

(2009) Raphael Kopan et al.   CELL

β-Secretase-1 elevation in transgenic mouse models of Alzheimer’s disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development

(2009) Xue-Mei Zhang et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

The  -Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential

(2009) R. Vassar et al.   JOURNAL OF NEUROSCIENCE

A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis

(2009) G. Di Fede et al.   SCIENCE

Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves

(2008) Xiangyou Hu et al.   FASEB JOURNAL

Abnormal axonal guidance and brain anatomy in mouse mutants for the cell recognition molecules close homolog of L1 and NgCAM-related cell adhesion molecule

(2008) A. Heyden et al.   NEUROSCIENCE

Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice

(2008) A. V. Savonenko et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BACE1 gene deletion: Impact on behavioral function in a model of Alzheimer's disease

(2007) Dione Kobayashi et al.   NEUROBIOLOGY OF AGING