Exploration of Aberrant E3 Ligases Implicated in Alzheimer’s Disease and Development of Chemical Tools to Modulate Their Function

Adaptors as the regulators of HECT ubiquitin ligases

(2021) Sonia Shalini Shah et al.   CELL DEATH AND DIFFERENTIATION

Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities

(2021) Marlene F. Schmidt et al.   CELL DEATH AND DIFFERENTIATION

Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

(2021) Qi Liu et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment

(2021) Xu Zhou et al.   CELLULAR AND MOLECULAR NEUROBIOLOGY

Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer’s disease risk variant p.S1038C in the TTC3 gene

(2021) Mayra Juliana Laverde-Paz et al.   Stem Cell Research

Role of Neuron and Glia in Alzheimer’s Disease and Associated Vascular Dysfunction

(2021) Sanghamitra Bandyopadhyay   Frontiers in Aging Neuroscience

Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases

(2021) Soonsil Hyun et al.   Life-Basel

Strategies in the design and development of (TAR) DNA-binding protein 43 (TDP-43) binding ligands

(2021) Praveen P.N. Rao et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

TNF receptor associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation

(2020) Sabrina Semmler et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond

(2020) Bo Zhao et al.   PHARMACOLOGICAL REVIEWS

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

(2020) Zixin Hu et al.   Scientific Reports

The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease

(2020) Martí Colom-Cadena et al.   Alzheimers Research & Therapy

Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases

(2020) Qian Cai et al.   Cells

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

(2020) Wenzhang Wang et al.   Molecular Neurodegeneration

PROTAC Compounds Targeting α-Synuclein Protein for Treating Neurogenerative Disorders: Alzheimer’s and Parkinson’s Diseases

(2020) Robert B. Kargbo   ACS Medicinal Chemistry Letters

Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10

(2020) Gwen R. Buel et al.   Nature Communications

Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer’s disease patients, animal models and cell models

(2020) Zhimin Long et al.   Aging-US

The Role of Tissue-Specific Ubiquitin Ligases, RNF183, RNF186, RNF182 and RNF152, in Disease and Biological Function

(2020) Takumi Okamoto et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Aberrant activation of neuronal cell cycle caused by dysregulation of ubiquitin ligase Itch results in neurodegeneration

(2020) Monika Chauhan et al.   Cell Death & Disease

The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders

(2020) Asia Owais et al.   Cancers

CHIP as a therapeutic target for neurological diseases

(2020) Shuo Zhang et al.   Cell Death & Disease

Ubiquitin homeostasis is disrupted in TDP-43 and FUS cell models of ALS

(2020) Natalie E. Farrawell et al.   iScience

Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective

(2020) François Le Guerroué et al.   CELL DEATH AND DIFFERENTIATION

Fragment-based covalent ligand screening enables rapid discovery of inhibitors for the RBR E3 ubiquitin ligase HOIP

(2019) Henrik Johansson et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

(2019) Blake E. Smith et al.   Nature Communications

Structural and Functional Characterization of Ubiquitin Variant Inhibitors of USP15

(2019) Joan Teyra et al.   STRUCTURE

First targeted protein degrader hits the clinic

(2019) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models

(2019) M Catarina Silva et al.   eLife

HECT E3 Ligases: A Tale With Multiple Facets

(2019) Janine Weber et al.   Frontiers in Physiology

Targeted protein degradation: elements of PROTAC design

(2019) Stacey-Lynn Paiva et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases

(2019) Matthew Ravalin et al.   Nature Chemical Biology

The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation

(2019) Heng Lin et al.   Frontiers in Immunology

The E3 Ubiquitin Ligase MARCH8 Regulates TNF‐α‐Induced Apoptosis in Hippocampal Neurons by Targeting Myosin Light Chain 2 for Degradation

(2019) Shanglin Guo et al.   Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology

The E3 ubiquitin ligase CHIP in normal cell function and in disease conditions

(2019) Tingyu Wang et al.   Annals of the New York Academy of Sciences

Targeting the Synapse in Alzheimer’s Disease

(2019) Johanna Jackson et al.   Frontiers in Neuroscience

Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer’s Disease Pathogenesis

(2019) Anushka Chakravorty et al.   Frontiers in Aging Neuroscience

The many substrates and functions of NEDD4-1

(2019) Xi Huang et al.   Cell Death & Disease

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

(2019) Georgia R. Frost et al.   Frontiers in Aging Neuroscience

Roles of TRAF6 in central nervous system

(2018) Yang Dou et al.   Current Neuropharmacology

Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway

(2018) Mengchen Lu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Quantitative proteomics reveals neuronal ubiquitination of Rngo/Ddi1 and several proteasomal subunits by Ube3a, accounting for the complexity of Angelman syndrome

(2018) Juanma Ramirez et al.   HUMAN MOLECULAR GENETICS

Amyloid-β Induces AMPA Receptor Ubiquitination and Degradation in Primary Neurons and Human Brains of Alzheimer’s Disease

(2018) Yanmin Zhang et al.   JOURNAL OF ALZHEIMERS DISEASE

Targeting TRAF6 E3 ligase activity with a small molecule inhibitor combats autoimmunity

(2018) Jara Kerstin Brenke et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and Model Systems Revealed by Digital Snapshot Proteomics

(2018) Alban Ordureau et al.   MOLECULAR CELL

Mechanism of parkin activation by phosphorylation

(2018) Véronique Sauvé et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Mechanism of parkin activation by phosphorylation

(2018) Véronique Sauvé et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

(2018) Md. Sahab Uddin et al.   Frontiers in Aging Neuroscience

Neuronal Proteomic Analysis of the Ubiquitinated Substrates of the Disease-Linked E3 Ligases Parkin and Ube3a

(2018) Aitor Martinez et al.   Biomed Research International

Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer

(2018) Karan Bhuripanyo et al.   Science Advances

Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease

(2018) Eleanor K. Pickett et al.   ACTA NEUROPATHOLOGICA

Developing small-molecule inhibitors of HECT-type ubiquitin ligases for therapeutic applications: challenges and opportunities

(2018) Dan Chen et al.   CHEMBIOCHEM

Structure of TRAF Family: Current Understanding of Receptor Recognition

(2018) Hyun H. Park   Frontiers in Immunology

Proteolysis Targeting Chimera (PROTAC): A Paradigm-Shifting Approach in Small Molecule Drug Discovery

(2018) Pingyuan Wang et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

A cell-based high-throughput screening method based on a ubiquitin-reference technique for identifying modulators of E3 ligases

(2018) Maoyuan Tian et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma

(2017) Yi-Min Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1δE9 mouse model of Alzheimer’s disease

(2017) Brijesh Kumar Singh et al.   HUMAN MOLECULAR GENETICS

Molecular basis of interactions between SH3 domain-containing proteins and the proline-rich region of the ubiquitin ligase Itch

(2017) Guillaume Desrochers et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

UbMES and UbFluor: Novel probes for ring-between-ring (RBR) E3 ubiquitin ligase PARKIN

(2017) Sungjin Park et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mechanism of ubiquitin chain synthesis employed by a HECT domain ubiquitin ligase

(2017) Michael E. French et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002 reduces neuroinflammation

(2017) Suzanne A. B. M. Aarts et al.   Journal of Neuroinflammation

A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants

(2017) Mads Gabrielsen et al.   MOLECULAR CELL

Chemical Methods to Knock Down the Amyloid Proteins

(2017) Na Gao et al.   MOLECULES

Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3

(2017) Stefan Schoebel et al.   NATURE

Identifying the ubiquitination targets of E6AP by orthogonal ubiquitin transfer

(2017) Yiyang Wang et al.   Nature Communications

The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1

(2017) Adam J. Middleton et al.   Nature Communications

Tau association with synaptic vesicles causes presynaptic dysfunction

(2017) Lujia Zhou et al.   Nature Communications

Hydrophobic tagging-mediated degradation of Alzheimer's disease related Tau

(2017) Na Gao et al.   RSC Advances

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

(2017) Arun Upadhyay et al.   Frontiers in Molecular Neuroscience

Autophagy flux in CA1 neurons of Alzheimer hippocampus: Increased induction overburdens failing lysosomes to propel neuritic dystrophy

(2016) Matteo Bordi et al.   Autophagy

Systematic approaches to identify E3 ligase substrates

(2016) M. Iconomou et al.   BIOCHEMICAL JOURNAL

The Nedd4–1 WW Domain Recognizes the PY Motif Peptide through Coupled Folding and Binding Equilibria

(2016) Vineet Panwalkar et al.   BIOCHEMISTRY

Types of Ubiquitin Ligases

(2016) Francesca Ester Morreale et al.   CELL

Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1

(2016) Elizabeth M. Rodrigues et al.   JOURNAL OF NEUROSCIENCE

System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes

(2016) Wei Zhang et al.   MOLECULAR CELL

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Structural insights into the catalysis and regulation of E3 ubiquitin ligases

(2016) Lori Buetow et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

UbFluor: a mechanism-based probe for HECT E3 ligases

(2016) David T. Krist et al.   Chemical Science

Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity: implications for Parkinson’s disease

(2016) Mercè Canal et al.   Oncotarget

Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation

(2016) Masayuki Kaneko et al.   Scientific Reports

Parkin Regulation and Neurodegenerative Disorders

(2016) Cheng-Wu Zhang et al.   Frontiers in Aging Neuroscience

Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases

(2016) Qiuyang Zheng et al.   Frontiers in Aging Neuroscience

A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?

(2016) Vibhuti Joshi et al.   Frontiers in Molecular Neuroscience

The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer’s Disease and Spinal Cord Injury

(2016) Bing Gong et al.   Frontiers in Molecular Neuroscience

A Generic Platform for Cellular Screening Against Ubiquitin Ligases

(2016) Timurs Maculins et al.   Scientific Reports

Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis

(2015) Kirsten L. Viola et al.   ACTA NEUROPATHOLOGICA

CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of β-secretase

(2015) Amir Kumar Singh et al.   AGING CELL

Structural basis for the regulatory role of the PPxY motifs in the thioredoxin-interacting protein TXNIP

(2015) Y. Liu et al.   BIOCHEMICAL JOURNAL

Ubiquitin-Activated Interaction Traps (UBAITs) identify E3 ligase binding partners

(2015) H. F. O'Connor et al.   EMBO REPORTS

Parkin structure and function

(2015) Marjan Seirafi et al.   FEBS Journal

NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease

(2015) V. Corsetti et al.   HUMAN MOLECULAR GENETICS

Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains

(2015) Xuan Ye et al.   HUMAN MOLECULAR GENETICS

Multifaceted role of the ubiquitin ligase Itch in immune regulation

(2015) K Venuprasad et al.   IMMUNOLOGY AND CELL BIOLOGY

Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation

(2015) Christopher Riling et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Small Molecule CD40–TRAF6 Inhibitors

(2015) Barbara Zarzycka et al.   Journal of Chemical Information and Modeling

A Small Molecule That Switches a Ubiquitin Ligase From a Processive to a Distributive Enzymatic Mechanism

(2015) Stefan G. Kathman et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

Protein ubiquitination and formation of polyubiquitin chains without ATP, E1 and E2 enzymes

(2015) Sungjin Park et al.   Chemical Science

UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

(2015) Jiandong Sun et al.   Cell Reports

RBR E3 ubiquitin ligases: new structures, new insights, new questions

(2014) Donald E. Spratt et al.   BIOCHEMICAL JOURNAL

RBR E3-ligases at work

(2014) J. J. Smit et al.   EMBO REPORTS

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

(2014) Carles Galdeano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

(2014) Eric S. Fischer et al.   NATURE

Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation

(2014) Xuelai Fan et al.   NATURE NEUROSCIENCE

Effects of Oxidative Stress on the Solubility of HRD1, a Ubiquitin Ligase Implicated in Alzheimer’s Disease

(2014) Ryo Saito et al.   PLoS One

ATP6V0C Knockdown in Neuroblastoma Cells Alters Autophagy-Lysosome Pathway Function and Metabolism of Proteins that Accumulate in Neurodegenerative Disease

(2014) Leandra R. Mangieri et al.   PLoS One

Structural and Functional Framework for the Autoinhibition of Nedd4-Family Ubiquitin Ligases

(2014) Sara Mari et al.   STRUCTURE

High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy

(2014) M Rossi et al.   Cell Death & Disease

2-(4-Hydroxy-3-methoxyphenyl)-benzothiazole suppresses tumor progression and metastatic potential of breast cancer cells by inducing ubiquitin ligase CHIP

(2014) Hiromi Hiyoshi et al.   Scientific Reports

Ubiquitin proteasome system networks in the neurological disorders

(2013) Mrudhula Anuppalle et al.   Animal Cells and Systems

Structural and Biochemical Basis for Ubiquitin Ligase Recruitment by Arrestin-related Domain-containing Protein-3 (ARRDC3)

(2013) Shiqian Qi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Membrane-associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor

(2013) H. Fujita et al.   JOURNAL OF CELL SCIENCE

Amyloid-  Peptide Oligomers Disrupt Axonal Transport through an NMDA Receptor-Dependent Mechanism That Is Mediated by Glycogen Synthase Kinase 3  in Primary Cultured Hippocampal Neurons

(2013) H. Decker et al.   JOURNAL OF NEUROSCIENCE

Elevated TRAF2/6 expression in Parkinson’s disease is caused by the loss of Parkin E3 ligase activity

(2013) Ji-Yun Chung et al.   LABORATORY INVESTIGATION

Structure of Parkin Reveals Mechanisms for Ubiquitin Ligase Activation

(2013) J.-F. Trempe et al.   SCIENCE

A Strategy for Modulation of Enzymes in the Ubiquitin System

(2013) A. Ernst et al.   SCIENCE

Emerging roles of E3 ubiquitin ligases in autophagy

(2013) Ersheng Kuang et al.   TRENDS IN BIOCHEMICAL SCIENCES

Hrd1 Facilitates Tau Degradation and Promotes Neuron Survival

(2012) Y.X. Shen et al.   CURRENT MOLECULAR MEDICINE

Upregulation of the E3 ligase NEDD4-1 by Oxidative Stress Degrades IGF-1 Receptor Protein in Neurodegeneration

(2012) Y.-D. Kwak et al.   JOURNAL OF NEUROSCIENCE

Protein homeostasis and aging: Role of ubiquitin protein ligases

(2012) Nihar Ranjan Jana   NEUROCHEMISTRY INTERNATIONAL

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

(2012) Thangiah Geetha et al.   NEUROCHEMISTRY INTERNATIONAL

Ubiquitin Ligase Substrate Identification through Quantitative Proteomics at Both the Protein and Peptide Levels

(2011) Kimberly A. Lee et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A

(2011) Alexander Lemak et al.   JOURNAL OF BIOMOLECULAR NMR

Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking

(2011) Amy Lin et al.   JOURNAL OF NEUROCHEMISTRY

Small-molecule displacement of a cryptic degron causes conditional protein degradation

(2011) Kimberly M Bonger et al.   Nature Chemical Biology

Ubiquitin ligase Nedd4 promotes  -synuclein degradation by the endosomal-lysosomal pathway

(2011) G. K. Tofaris et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway

(2010) Philip J. Dolan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Loss of HRD1-Mediated Protein Degradation Causes Amyloid Precursor Protein Accumulation and Amyloid-  Generation

(2010) M. Kaneko et al.   JOURNAL OF NEUROSCIENCE

The art of the chemical probe

(2010) Stephen V Frye   Nature Chemical Biology

Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development

(2010) Hiroshi Kawabe et al.   NEURON

E3 Ligase Nedd4 Promotes Axon Branching by Downregulating PTEN

(2010) Jovana Drinjakovic et al.   NEURON

The E3 Ligase TTC3 Facilitates Ubiquitination and Degradation of Phosphorylated Akt

(2009) Futoshi Suizu et al.   DEVELOPMENTAL CELL

ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology

(2009) Antero Salminen et al.   Journal of Neuroinflammation

E2 interaction and dimerization in the crystal structure of TRAF6

(2009) Qian Yin et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Aggresome Formation and Neurodegenerative Diseases: Therapeutic Implications

(2008) L. Chin et al.   CURRENT MEDICINAL CHEMISTRY

Novel Functions of Ubiquitin Ligase HRD1 With Transmembrane and Proline-Rich Domains

(2008) Tomohiro Omura et al.   JOURNAL OF PHARMACOLOGICAL SCIENCES

A novel brain-enriched E3 ubiquitin ligase RNF182 is up regulated in the brains of Alzheimer's patients and targets ATP6V0C for degradation

(2008) Qing Liu et al.   Molecular Neurodegeneration